An Early Feasibility Study of the Safety and Efficacy of the Nucleus 24 Auditory Brainstem Implant in Children With Cochlear or Cochlear Nerve Disorders Not Resulting From Neurofibromatosis Type II
Phase: NA
Conditions: Developmental Cochlear Nerve Deficiency, Acquired Cochlear Nerve Deficiency, Cochlear Aplasia, Post-meningitis Cochlear Ossification, Cochlear Malformation
Sponsor: University of North Carolina, Chapel Hill

 
An Early Feasibility Study of the Safety and Efficacy of the Nucleus 24 
Auditory Brainstem Implant in Children with Cochlear or Cochlear 
Nerve Disorders Not Resulting from Neurofibromatosis type II 
 
 
 
NCT number NCT01904448 
Document Date June 30, 2012 
 

Nucleus 24 ABI in Non-NFII Children 
 
1 
An Early Feasibility Study of the Safety and Efficacy of the Nucleus 24 Auditory Brainstem 
Implant in Children with Cochlear or Cochlear Nerve Disorders Not Resulting from 
Neurofibromatosis type II 
 
 
Craig A. Buchman, MD (Principal Investigator and Sponsor) Professor, Vice Chair for Clinical 
Affairs, Medical Director of the Carolina Children’s Communicative Disorders Program, 
Department of Otolaryngology-Head & Neck Surgery, G190 Physician’s Office Bldg., 170 
Manning Drive, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7600 
Tel: 919-843-4820 
Fax: 919-843-4750 
Email: buchman@med.unc.edu 
 
Matthew G. Ewend, MD, Professor and Chair, Department of Neurosurgery, University of North 
Carolina at Chapel Hill, Chapel Hill, NC 27599 
Tel: 919-966-1374 
 
 
 
Email: ewend@med.unc.edu 
 
Holly FB Teagle, AuD, Associate Professor and Director of the Carolina Children’s 
Communicative Disorders Program (CCCDP), Department of Otolaryngology-Head & Neck 
Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7600 
Tel: 919-419-1449 
  
 
 
Email: holly_teagle@med.unc.edu 
 
Patricia A. Roush, AuD, Associate Professor and Director of Pediatric Audiology, Department of 
Otolaryngology-Head & Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, 
NC 27599-7600. 
Tel: 919-966-6485 
 
 
 
Email: proush@unch.unc.edu 
 
Shuman He, PhD, Assistant Professor, Department of Otolaryngology-Head & Neck Surgery, 
University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7600. 
Tel: 919-419-1449 
 
 
 
Email: shuman_he@med.unc.edu 
 
John H. Grose, PhD, Professor, Department of Otolaryngology-Head & Neck Surgery, 
University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7600. 
Tel: 919-966-9777 
 
 
 
Email: john_grose@med.unc.edu 
 
Sponsor:  
Craig A. Buchman, MD 
 
IRB:  
 
 
 
 
 
 
 

Nucleus 24 ABI in Non-NFII Children 
 
2 
Study Objective 
 
The purpose of this feasibility study is to demonstrate the safety and efficacy of the 
Nucleus 24 Multichannel Auditory Brainstem Implant (ABI, Cochlear Corp, Sydney, AUS) in 
children who do not have the diagnosis of neurofibromatosis type II (NFII), and who have either 
experienced failed cochlear implantation (CI) or have been unable to receive a CI secondary to 
cochlear or cochlear nerve disorders. These conditions can include: developmental or acquired 
cochlear nerve deficiency (CND), cochlear aplasia (Michel), post-meningitis cochlear 
ossification, or cochlear malformation. This study proposes to implant up to 10 pre-linguistic 
young children (18 mos to 5 yrs. of age) and 5 post-linguistic children (<18 yrs of age) with the 
Nucleus 24 Multichannel ABI in an attempt to demonstrate safety of the surgical procedure, 
tolerance of device stimulation, and the potential for auditory benefit beyond that experienced 
with their CI. This study will provide the preliminary experience for a larger scale clinical trial. 
 
Regulatory Status of the Investigational Device 
 
Data supporting the safety and effectiveness of the Nucleus 24 ABI were provided to the 
United States Food and Drug Administration (FDA) in March 2000, as part of a Premarket 
Approval Application. On July 21, 2000, the Agency’s Ear, Nose and Throat (ENT) Advisory 
Panel unanimously recommended that FDA release the Nucleus 24 ABI for use by individuals 
with NFII above the age of 11 years. Cochlear Americas received a letter of approval from the 
Agency in October 2000 (PMA No P000015). The letter is enclosed.  
 
The Nucleus 24 ABI features a multichannel electrode lead that terminates in twenty-one, 
0.7 mm platinum disk-electrodes. The 21 platinum contacts are arranged on the surface of a 
silicone rubber pad in three rows of seven contacts and are surgically placed on the surface of the 
brainstem; specifically, on the surface of the cochlear nucleus. 
 
Background and Rationale 
 
According to Stone, “Hearing impairment strikes at the very essence of being human, 
because it hinders communication with others” (1). Children born deaf (i.e. pre-linguistic 
deafness) have severe delays in speech and language acquisition that can retard their social and 
emotional development, influencing educational and career attainment (2). The pre-linguistic 
deafened child seldom develops significant understandable speech, and is often socially 
stigmatized by those in the hearing world (3). Thus, individuals with untreated congenital 
deafness are often integrated into a separate “deaf community.” Hearing impairment negatively 
impacts upon educational attainment, employment opportunities, income, healthcare utilization, 
and life expectancy (1, 4-15). As most deaf children are educated outside of the mainstream 
setting and ultimately achieve lesser levels of employment and income, lifetime losses for having 
untreated severe to profound hearing loss have been estimated at over $1 million dollars per 
child ($297,000 added expenditures) (16-18). By comparison, these lifetime costs are 
significantly higher than for near drowning ($98,500), accidents from firearms ($89,100), stroke 
($129,200), rheumatoid arthritis ($130,500), and epilepsy ($172,900), and are similar to those for 
the devastating illness of schizophrenia ($295,000). In addition to cost, deafness also contributes 
to an increased risk for depression, anxiety, and physical dysfunction (7, 8 19-21). In summary, 
untreated deafness is a major disability that negatively impacts upon all aspect of life. 

Nucleus 24 ABI in Non-NFII Children 
 
3 
 
A CI is an auditory, neural stimulating prosthesis. These devices use a multiple electrode 
array that is inserted into the cochlea to electrically stimulate the auditory (i.e. cochlear) nerve in 
cases of severe to profound hearing loss. Using specialized speech processing and encoding 
strategies, these devices can restore sound awareness and significantly improve speech 
perception in both quiet and noise. Improved speech perception restores communication for 
adults and allows children to develop spoken language (22, 23). Thus, CIs alleviate many of the 
disabling effects of deafness described above. In addition to quality of life benefits, the cost-
utility of this intervention is positive for both adults and children (24, 25). 
 
The only absolute contraindication to CI is an absent cochlea or an absent cochlear nerve. 
In addition, patients at risk for lower levels of performance include those with anatomic 
conditions that adversely affect the electrode-neural interface such as developmental labyrinthine 
malformations and cochlear ossification and fibrosis secondary to meningitis. While the 
diagnosis of cochlear (i.e. Michel) aplasia is clear clinically, the diagnosis of cochlear nerve 
aplasia is made somewhat more challenging by the spatial resolution of current imaging 
modalities (26-29). Because of this uncertainty, the term cochlear nerve deficiency (CND) was 
coined to refer to the situation where the cochlear nerve is small or absent on high resolution 
magnetic resonance imaging (MRI), or where the bony cochlear nerve aperture and canal are 
small or absent on temporal bone computed tomography (CT). The clinical diagnosis of CND 
includes these imaging findings in the setting of profound hearing loss (29, 30). Auditory 
brainstem response testing that shows a present cochlear microphonic but absent neural waves 
can support the diagnosis (29). 
 
In an effort to provide hearing to deaf children who have inner ear malformations, CND, or 
ossification from meningitis, CI has been undertaken over the years (30). This might be 
considered the standard of care today for those who desire spoken language communication. 
Results of these interventions suggest that most children with CND gain some sound awareness 
from these devices using higher levels of electrical stimulation. However, achievement of open 
set speech perception for the purposes of speech and language development has been largely 
unsuccessful, probably as a result of a poor electrode-neural interface and other associated 
conditions (30-33). In the study from our institution, only 19% of children with CND developed 
any open set speech perception using their CI, and none of these children were able to 
communicate using auditory-only information (i.e. all used some supplemental sign language). 
 
The ABI is an electronic device designed to convert environmental sounds into electrical 
impulses that are delivered along a multiple electrode array situated in close proximity to the 
cochlear nucleus in the brainstem. In a manner similar to the cochlear nerve, the cochlear nucleus 
maintains some degree of tonotopic arrangement; thus, application of discrete electrical 
stimulation along certain spatial locations within the lateral recess of the 4th ventricle results in 
discriminable psychophysical frequency percepts (i.e. pitch). The ABI is indicated for patients 
where the cochlear nerve is absent or unavailable for stimulation bilaterally. Most commonly, 
adults and children with hearing loss secondary to NFII with bilateral acoustic (8th nerve) tumors 
have been the main group of patients implanted to date.  
 
In general, outcomes from ABI can be described in terms of sound detection and speech 
perception abilities using closed- and open-set test materials with and without the addition of lip-

Nucleus 24 ABI in Non-NFII Children 
 
4 
reading. In a recent review of 86 NFII patients implanted with ABIs, 13 did not respond to 
stimulation and 1 was explanted (34). Of the 60 patients with available 6-month data, mean 
open-set speech perception scores (CUNY sentences) using the implant alone, vision alone, and 
both the implant and vision on CUNY sentence were <10%, 30%, and nearly 55% correct. 
However, there was a wide range of auditory abilities, with some patients obtaining combined 
vision and sound scores of >90% correct (34). Thus, in patients with NFII, the ABI is an 
excellent enhancement to lip-reading. For individuals that have known only spoken language 
throughout their entire life, this connection to the speaking world is significant, and the 
importance of this communication enhancement should not be underestimated.  
 
Experience with Auditory Brainstem Implantation in Patients without NFII 
 
The effectiveness of ABI for patients without NFII has only recently been explored (35-43). 
Colletti et al. in Verona, Italy, have summarized their results of a group of adult patients with a 
variety of conditions (excluding NFII) that received an ABI between 1997 and 2007 (40). 
Results were compared to a group of 34 individuals with NFII implanted by the same surgeon. 
The duration of deafness ranged from 3.2 to 8.5 years (X = 5.1; SD = 2.4) for the NFII group and 
ranged from 1.2 to 19.8 years (X = 9.6; SD = 5.9) for non-NFII group. All non-NFII patients 
were implanted through a retrosigmoid craniotomy. NFII patients also required tumor removal 
prior to placement of the ABI. 
 
After at least one year of device use, using audition alone, sentence recognition ranged 
from 10 to 100% (X  = 59%; Median = 53%; SD = 21.34) in the non-NFII group (n = 48) and 
from 5 to 31% (X  = 10%; Median = 16%; SD = 15.21) in the NFII group (n = 32). These values 
were significantly better (p  = 0.0007) in the non-NFII subgroup. Table 1 below, adapted from 
Colletti et al (2009), shows the sentence recognition score (type not specified) outcomes for the 
various etiologies without NFII (40). Except for those adults with auditory neuropathy, sentence 
recognition scores in these adult patients are significantly better than in the patients with NFII. 
 
TABLE 1. Open-set sentence recognition 1-10 yrs. after ABI.  
 
 
 
 
 
Cause   
 
No. Subjects  
Range,  % X      SD  
  T versus NT  
t test 
 
 
Head trauma  
     
        7   
32-80    62  
57  
        23,41            p = 0.005 
Auditory neuropathy  
        4   
12-18    15  
16  
         2,52             p = 0.07 
Cochlear malformations            6   
37-61    44  
61  
         11,2             p = 0.006 
Altered cochlear patency          31   
34-100    60  
64  
        19,81            p = 0.0048 
 
x-mean; Med-median, sd-standard deviation, T-tumor (NFII), NT-non-tumor 
 
 
 
 
 
Based on these results, the investigators concluded that adults with acquired conditions that 
are isolated to the cochlea or cochlear nerve such as otosclerosis (altered cochlear patency) and 
traumatic cochlear nerve avulsion are better candidates for ABI success than those individuals 
with NFII. They hypothesized that NFII and/or its treatment results in pathological changes in 
the brainstem and cochlear nuclei that might preclude good performance with an ABI. Similarly, 
congenital malformations and auditory neuropathy might produce central nervous system 
changes that are not conducive to the development of open set speech perception using an ABI, 
possibly as a consequence of long-term auditory deprivation. 
 
In theory, children would be better candidates than adults for an ABI since they have 
substantial developmental plasticity and have no auditory memory that requires precise matching 

Nucleus 24 ABI in Non-NFII Children 
 
5 
of signals. Colletti and colleagues in Verona, Italy, have placed ABIs in children without NFII 
and have summarized their experience in 2008 (41). In that study, 26 children (17 in Verona; 9 in 
other countries) aged 14 months to 16 years received an ABI for different tumor and non-tumor 
diseases between 1996 and 2006. Etiologies included cochlear nerve aplasia with or without 
associated inner ear malformations (n=19), NFII (n=2), incomplete cochlear partition (n=2), 
auditory neuropathy (n=1), post-meningitis ossification (n=1), and temporal bone fracture with 
nerve avulsion (n=1). Fourteen children had a variety of other disabilities including: mild motor 
delay (n=8), learning disability (n=7), behavioral impairment (n=7), cognitive delay (n=8), 
language delay (n=6), and 2 with visual impairment. Six children received previous CIs with no 
auditory results. All were operated through a retrosigmoid craniotomy, and there was one 
reported major complication (detailed below). Results showed that all children consistently use 
their devices (avg. 8 hrs./day) and demonstrated gradual improvement in communication skills, 
showing more attention and interest in school and at home. From an auditory perspective, 20 pre-
linguistic and 4 post-linguistic children have environmental sound awareness, detection of 
instrumental sounds and lip-reading enhancement; 3 pre-linguistic and 2 post-linguistic children 
achieved bi-syllabic word recognition as well as understanding of simple commands, but only 
one post-linguistic child had open set recognition (average 50% correct responses) and can 
perform the speech tracking test. Cognitive testing in a subset of 9 children using the ABI 
demonstrated improved selective visual-spatial attention (form completion subtest) and fluid 
(multisensory) reasoning (repeated patterns subtest) when compared to a group of 4 congenitally 
deaf children without an auditory assistive device. 
 
Sennaroglu et al. implanted 6 children with severe inner ear malformations using the 
Nucleus 24 ABI. These children gained basic auditory function and were able to recognize and 
discriminate sounds such as the doorbell and telephone by the third month of usage. Two 
children had developed open set discrimination scores at that time (42). As of 2011, 21 children 
had received the same ABI for inner ear malformations in the same implant center in Turkey. No 
child has been unresponsive to implantation, and the number of active electrodes ranges from 8 
to 20. Five children are reported to have variable degrees of open set speech perception (no 
details). When the pre- and post-operative linguistic gap (receptive and expressive) are compared, 
the majority had either decreased or stabilized the gap suggesting that ABI is effective in the 
language development of these children. Almost all children where the gap still increased in spite 
of ABI had additional handicaps. It was concluded that the presence of additional handicaps is 
the most important limiting factor in the language development of ABI in children with severe 
malformations (43). 
 
A child implanted in Verona was seen at the University of North Carolina at Chapel Hill 
(UNC) in 12/2009 for evaluation. He was implanted at 3 yrs. of age for CND with the Nucleus 
24 Multichannel ABI through a retrosigmoid approach. His MRI and CT confirmed the anatomic 
findings and audiometric testing without his device revealed a profound hearing loss. After 
nearly 4 years of implant use (7 yrs. of age), the child scored 100% on an ESP-monosyllabic 
word test (12-choice, closed set pictures) and 81% and 48% on PBK phoneme and word scores 
(open set without visual cues), respectively.  Evaluation by our team speech pathologist revealed 
that the child was a functional spoken language user in that he was able to produce complex 
sentence structure, although he did have some articulation errors that appeared to be related to 
oral-motor deficiencies. He could actively argue with his older brother in the exam room using 
oral language alone. 

Nucleus 24 ABI in Non-NFII Children 
 
6 
 
In summary, the ABI appears to provide auditory awareness in all children. Emerging data 
suggest that some children without significant associated handicaps are beginning to develop 
open set speech perception and oral language. While further study is clearly needed, this 
approach appears promising for the limited subset of deaf children who cannot benefit from a CI. 
 
Complications from Auditory Brainstem Implantation 
 
Complications related directly to the ABI have been unusual. Toh and Luxford indicated 
the most common complications in ABI surgery appear to be cerebrospinal fluid (CSF) leak, 
electrode migration, and non-auditory side effects during stimulation (44). Fatal complications 
are exceedingly rare. Laszig et al. reported one NFII patient that died following tumor removal 
and ABI insertion as a result of pulmonary embolism and pneumonia (45). Grayelli et al. also 
reported one fatal embolism (46). These complications were more likely related to extended 
duration posterior fossa surgery rather than ABI surgery, specifically. Electrode migration 
appears to be a complication that occurs in patients undergoing ABI in the setting of tumor 
removal where distorted brainstem anatomy results in a shallow or deformed lateral recess. 
Following surgery, brain re-expansion might displace the electrode.  
 
CSF leaks are an expected risk from any surgery where CSF is encountered. Otto et al 
reported 2 CSF leaks among 61 patients following translabyrinthine tumor removal and ABI 
placement that resolved with either a pressure dressing or a temporary lumbar subarachnoid 
drain (47). Grayelli et al. also reported 2 cases of CSF leaks after 31 ABI surgeries, and 
Sennaroglu et al. reported one case of a CSF leak in a child who underwent retrosigmoid ABI 
placement that resolved with wound exploration and repair of the air cell opening (42, 43).  
 
Colletti et al reported on 114 ABI operations performed through the retrosigmoid approach 
in Verona from 1997 to 2008 in 83 adults and 31 children (48). Thirty-six had NFII (34 adults 
and 2 children), and 78 (49 adults and 29 children) had cochlear or cochlear nerve disorders 
unrelated to NFII. Table 2 below details the complications from this study. There was a 
statistically lower risk for complications among the patients without NFII, presumably because 
there was no need for tumor removal prior to device placement. Importantly, there was 1 major 
complication in a child implanted in Manchester, England. That child developed a cerebellar 
contusion and swelling requiring a return to the operating room for clot evacuation. This child 
recovered without neurological sequelae.  
 
Other complications in children included wound seroma (n=4) that were managed with 
aspiration and bandage, minor wound erythema treated with antibiotics alone, and transient 
balance problems that resolved without treatment. 
 
Non-auditory side effects are a relatively common occurrence from ABI stimulation and 
are usually related to activation of the neural tissue in the region of the implant. Toh and Luxford 
reported non-auditory side effects in 42% of multichannel ABI users (44). Colletti et al (48) 
reported that ipsilateral body tingle was observed in 2 children (6.9%), facial nerve stimulation in 
2 (6.9 %), dizziness in 1 (3.4%), headache in 1 (3.4%), and throat tingle/tickle in 1 (3.4%) child. 
In adults, ipsilateral body tingle was observed in 10 subjects (8.7%: 7 NFII and 3 non-tumor), 
facial nerve stimulation in 6 (5.2%: 4 NFII and 2 non-tumor), dizziness in 15 (19%: 9 NFII and 6 

Nucleus 24 ABI in Non-NFII Children 
 
7 
non-tumor), headache in 5 (6 %: 3 NFII and 2 non-tumor), and throat tingle/tickle in 8 (9.6%: 5 
NFII and 3 non-tumor). These side effects are all alleviated with selective electrode deactivation. 
Re-activation of the offending electrode over time usually resolved the issue. 
 
TABLE 2. Complications in ABI patients. 
 
 
 
 
  
NFII 
 
Non-tumor 
 
 
 
 
 
Ad  
  
Ad  
Ch 
 
Major complications  
 
 
 
Mortality (unrelated to ABI) 
3  
 
0  
0 
Cerebellar contusion  
 
1  
 
0  
1 
Permanent facial palsy  
 
1  
 
0  
0 
Meningitis  
 
 
1  
 
2a  
1a 
Lower cranial neuropathy  
2  
 
0 
0 
Hydrocephalus   
 
1  
 
1  
0 
Pseudomeningocele  
 
2  
 
0  
0 
Cerebrospinal fluid leakage  
6  
 
1 
0 
 
Minor complications 
Transient hydrocephalus   
7  
 
1  
0 
Wound seroma   
 
4  
 
2  
4 
Minor infections   
 
2  
 
2  
1 
Balance problems  
 
11  
 
2  
1 
Infection around implant   
2  
 
2  
0 
Infection surgical flap  
 
2  
 
1  
0 
Transient facial palsy  
 
8  
 
0  
0 
Temporary dysphonia and  
difficulty in swallowing 
 
0  
 
0  
1 
Headache  
 
 
8  
 
3  
0 
Flap problems  
 
 
2  
 
0  
0 
  
Non-auditory side effects   
28  
 
16  
7 
 
 (a) Approximately 2 years after ABI activation. 
 Ad, adults; Ch, children.  
 
 
 
 
 
 
 
 
 

Nucleus 24 ABI in Non-NFII Children 
 
8 
Benefits and Risks 
 
The benefits and risks of ABI in children are listed in TABLE 3 based on a compilation of 
previous literature using the ABI in the proposed population, personal experience with posterior 
fossa surgery at UNC and in the literature, and the experience of children that have received 
cochlear implants for severe to profound hearing loss. The sections above detail the outcomes 
from the medical literature and the individual benefits and risks as well as others not previously 
mentioned are in the table below. 
 
TABLE 3. Potential Benefits and Risks of ABI  
Potential Benefits 
Potential Risks 
 
Hearing: 
o 
Sound awareness 
o 
Speech perception 
 
Sound awareness 
 
Closed-set 
 
Open-set 
o 
Music appreciation 
 
Speech and Language Acquisition  
 
Enhanced Communication 
o 
Oral 
o 
Improved lip-reading 
o 
Total 
 
Educational Achievement 
 
Employment Opportunities 
 
Quality of Life 
 
Reduced Costs secondary to: 
o 
Mainstream Education 
o 
Meaningful Employment 
 
 
Vascular injury with  
o 
Bleeding,  
 
Epidural hematoma 
 
Subdural hematoma 
 
Subarachnoid hemorrhage 
 
Brain contusion,  
o 
Thrombosis 
 
Ischemic stroke 
 
Infection 
o 
Wound 
o 
Central nervous system 
 
Meningitis  
 
Cerebritis/Encephalitis 
 
Epidural Abscess 
 
Subdural empyema 
 
Brain abscess 
o 
Device 
 
Cranial nerve injury  
o 
Trigeminal nerve-facial numbness or pain 
o 
Facial nerve-paresis or paralysis  
o 
Cochlear nerve-hearing loss 
o 
Vestibular nerve-vertigo or imbalance 
o 
Glossopharyngeal/Vagus nerves-vocal fold paresis 
or paralysis, palatal paresis or paralysis, with 
resulting dysphagia, aspiration hoarseness 
o 
Spinal accessory nerve-shoulder dysfunction and 
winged scapula 
o 
Hypoglossal nerve-tongue deviation, dysarthria, and 
dysphagia 
 
Cerebrospinal fluid disorder 
o 
Leakage (wound or rhinorrhea) 
o 
Pseudomeningocele formation 
o 
Hydrocephalus 
 
Death 
 
 
Non-auditory stimulation from the device 
o 
Facial pain or twitching 
o 
Throat tickle, spasm, or pain 
o 
Shoulder twitching 
o 
Hemibody tingle 
 
 
Device Failure 
 

Nucleus 24 ABI in Non-NFII Children 
 
9 
Potential Benefits (see “Experience with Auditory Brainstem Implantation in Patients without NFII” for 
literature review). 
Children receiving the ABI in the present study have a very realistic chance for gaining 
improved sound awareness, enhanced lip reading, and limited closed set speech (pattern 
perception) understanding with the device. This has been previously demonstrated for both 
adults (>18 yrs of age) with and without NF2 as well as for children (<18 yrs) without NF2.  In 
most instances, this will represent a significant improvement over that obtained using their CI. 
Higher levels of closed set (words) and open set speech understanding have been demonstrated 
in some adults and children using the ABI. As age of implantation and the presence of 
developmental and cognitive delays negatively impact upon a child’s ability to achieve this level 
of performance, the chances of this outcome for children in the present study remain unknown 
since most of those implanted in other parts of the world had these complicating, negative 
prognostic factors. This study will actively control for these variables by only implanting 
younger (18 mo to 5 yrs) pre-linguisitc children without such delays or those that are post-
linguistic (< 18 yrs with previous open-set speech perception using a cochlear implant). Our 
group at UNC as well as others has personally tested children that have obtained significant 
open-set speech perception abilities using the ABI alone (implanted in Italy). As in CI, increased 
speech perception abilities can improve speech and language acquisition, educational 
achievement, employment opportunities and quality of life. These long-range benefits very much 
depend on the speech perception abilities of the child using the ABI device. If the device fails to 
provide sound awareness or improved speech understanding, then the remaining benefits are 
much less likely. 
 
Potential Risks (see “Complications from Auditory Brainstem Implantation” for a literature review) 
Risks and complications from ABI surgery are expected to be uncommon but can 
potentially be serious. Majors complications such as bleeding in or around the brain including 
major cerebellar contusion should be very unlikely since extensive dissection, such as is 
undertaken in tumor surgery, will be unnecessary. In tumor surgery, the risk of major bleeding is 
well below 2%. At UNC, we have had one major posterior fossa hemorrhage in our last 164 
acoustic tumor cases (0.6%). In a large series (n=4400) from the literature of non-tumor posterior 
fossa craniotomies performed for microvascular decompression, the risk of cerebellar injury 
(parenchymal bleeding/contusion) was less the 1% and major other hemorrhage was much less 
common. Thus, the risk for intracranial hemorrhage and/or cerebellar injury with subsequent 
stroke is small. CSF leakage from the wound or from the nose (rhinorrhea) can also occur. This 
will likely be the most common surgical complication. Given the lack of need for internal 
auditory canal drilling (as in acoustic neuroma surgery); the leak risk will be well below 10% 
(that seen for acoustic neuroma surgery in the literature). At UNC, our leak rate was <8% (n=13) 
for our last 164 acoustic tumor cases. In the microvascular decompression literature, the CSF 
leak rate is <2%. The etiology of rhinorrhea, should it occur, will also be very clear since internal 
auditory canal drilling is not required in this surgery. Rhinorrhea will arise from exposed mastoid 
air cells in the cranial opening. Similarly, the risk of cranial nerve injury will be unlikely since 
the anatomy will not be obscured by pathology such as tumors or infection. While cranial nerve 
8 and 9 border the lateral recess of the 4th ventricle (Foramen of Luschka), neural dissection will 
likely be mostly unnecessary and not obscured by tumor. Infection risk can include meningitis. 
This risk is less than 2% as a complication from craniotomy in the literature. The risk of device 
loss from infection is also very small.  
 

Nucleus 24 ABI in Non-NFII Children 
 
10
Non-auditory stimulation is expected to occur in roughly 20% of subject. Symptoms can 
include: facial pain or twitching, throat tickle, spasm, or pain, shoulder twitching, and hemibody 
tingle. Altering electrode maps and activation patterns can minimize or eliminate such 
stimulation. While not likely, there is the remote potential for large numbers of electrodes to 
require deactivation to the point that auditory stimulation will not be effective. Also, while not 
reported in this population, the theoretical possibility for cardiac arrest from stimulation along 
the lower cranial nerves.  
When balancing the benefits and risk of ABI surgery in children, there is no truly 
comparable surgical cohort for the population in question. However, when one considers 
microvascular decompression surgery for disorders such as trigeminal neuralgia and hemifacial 
spasm, the risks of ABI surgery are expectedly similar (and very low) and the potential benefits 
for the deaf child undergoing ABI far exceeds those benefits enjoyed by the vascular 
compression population. While facial pain and twitching are problematic for those with vascular 
compressive disorders, the impact of life-long deafness on a child are profound. As previously 
pointed out, children born deaf (i.e. pre-linguistic deafness) have severe delays in speech and 
language acquisition that can retard their social and emotional development, influencing 
educational and career attainment (2). The pre-linguistic deafened child seldom develops 
significant understandable speech, and is often socially stigmatized by those in the hearing world 
(3). Thus, individuals with untreated congenital deafness are often integrated into a separate 
“deaf community.” Hearing impairment negatively impacts upon educational attainment, 
employment opportunities, income, healthcare utilization, and life expectancy (1, 4-15). As most 
deaf children are educated outside of the mainstream setting and ultimately achieve lesser levels 
of employment and income, lifetime losses for having untreated severe to profound hearing loss 
have been estimated at over $1 million dollars per child ($297,000 added expenditures) (16-18). 
 
Protocol 
 
This study is an early feasibility study of the Nucleus 24 ABI in children without NFII. It 
will be conducted as a repeated-measures, single subject experiment with up to 10 replications 
(i.e. 10 total subjects). A single-subject research design was chosen (in which each subject serves 
as their own control) in order to accommodate the heterogeneity that is well known to 
characterize auditory prosthesis research. Post-operative evaluations will be conducted at the 
initial activation and at 1, 3, 6, 12, 18, 24, 30, and 36-month intervals post-activation. A 36-
month follow-up was chosen in an effort to demonstrate the emergence of open-set speech 
perception abilities prior to study cessation. Experience in the CI literature has shown that a 
minimum of 2 years of device usage is required for children with pre-lingual hearing impairment 
to develop some open-set speech perception abilities (50). Blinding or masking procedures are 
not included in the design, as the presence/absence of a brainstem implant cannot be easily 
concealed from the device recipients and/or clinical investigators.  
 
Preoperative measures will include high-resolution brain MRI, temporal bone CT and 
standardized, developmentally appropriate audiological and speech and language development 
test batteries. Children between 18 mo and 5 yrs of age with one of the anatomic conditions 
mentioned below and a present and patent cochlea will have previously received a CI as a 
precondition prior to consideration and will have demonstrated very limited to no benefit from 

Nucleus 24 ABI in Non-NFII Children 
 
11
the device based on a lack of development of significant closed set (more than pattern 
perception) or open set speech perception, and failure to achieve developmentally appropriate 
language growth during the follow up period. Those without a present or patent cochlea will be 
implanted with the ABI without the need for previous CI. Post-linguistic children (<18 yrs) will 
have had a CI but lost or lacked benefit from an appropriate CI and have no potential for revision 
CI surgery to improve their condition. The side/ear contralateral to the previous placed CI will be 
chosen, unless not possible (eg. bilateral CIs), to avoid potentially same-side, unwanted surgical 
and processor interactions as well as to allow comparison of performance in the follow-up period. 
If ABI needs to be considered ipsilateral to the previous CI, removal of the CI will need to be 
considered. Surgical interaction would be the issue of needing to operate in and around the CI 
device putting it at risk of damage. Unwanted processor interactions would be problematic if the 
receiver stimulator of the previous CI and the ABI were located in the same region. The ABI 
processor headpiece might be attracted to the CI receiver stimulator.  
 
Following implantation of the investigational device and at least 4-6 weeks of healing, the 
ABI will be activated in a controlled setting and auditory performance assessed at the previously 
proposed intervals (1, 3, 6, 12, 18, 24, 30, 36 months). Subjects will be evaluated using the 
Nucleus Speech Processor and programmed with an approved sound processing strategy. Post-
operative auditory function will be evaluated using behavioral audiometry and commonly used, 
developmentally appropriate measures of speech perception, speech production and language. 
Auditory function will also be assessed using electrophysiological tests at appropriate intervals. 
 
SPECIFIC AIMS 
Aim 1: Demonstrate the safety of ABI surgery in children. 
Aim 2: Demonstrate the development of sound awareness and improved speech 
understanding among children implanted with the ABI when compared to their baseline 
skills. 
Aim 3: Demonstrate the development of oral language skills following the use of the ABI 
that were not evident prior to its use. 
 
Methods and Subjects 
 
Up to 10 subjects will be enrolled in the study at the sponsoring location. Qualified subjects 
must meet the following inclusion criteria and must not exhibit any of the exclusion criteria.  
 
Inclusion Criteria 
 Pre-linguistic hearing loss (birth-5 yrs.; age at ABI 18 months-5yrs) with both: 
o MRI +/- CT evidence of one of the following:  
 Cochlear nerve deficiency  
 Cochlear aplasia or severe hypoplasia  
 Severe inner ear malformation 
 Post-meningitis ossification 
o When a cochlea is present or patent, lack of significant benefit from CI despite 
consistent use (>6 mo.) 
 No or limited speech perception ability (limited to pattern perception 
on closed set testing materials using the CI) 

Nucleus 24 ABI in Non-NFII Children 
 
12
 Lack of progress in auditory skills development 
18 months of age was chosen for the lower age limit to minimize the adverse effects of auditory 
deprivation on speech perception, speech production, and language development (23, 50). 
Moreover, 18 months of age will allow for a child to receive a CI at 1 year of age and have at 
least 6 months of device experience prior to considering ABI. Six months of CI usage prior to 
ABI consideration was chosen as this time period to allow for clear demonstration of lack of 
benefit as defined as either: (1) lack of sound awareness, or (2) where elevated charge 
requirements, absent ECAPs, elevated pure tone averages (>45 dB), and no or limited speech 
perception abilities are evident. To determine if a child is making significant progress both 
subjective and objective measures are used. Objectively, standardized speech perception, 
production, and language tests (as described below) are administered to determine if standard 
scores are following typical developmental patterns, even at a reduced rate. No or limited speech 
perception abilities will be considered when there are no improvement in IT-MAIS, or ESP 
measures from preop measures at the 6 month post-CI interval (30, 50). Developmental norms 
are also determined based on the hearing age. For example, a child who is 9 months old 
receptively understands between 3 and 50 vocabulary words and approximately 300 between the 
ages of 2 and 3. Does the child with a hearing age of 9 months understand this many words? For 
early speech development, all English vowels should be present by a hearing age of 12 months. 
Children 18 months of age can be tested using the standardized measures to determine progress.  
From a surgical perspective, 18 months of age is a sufficient size and weight in most instances to 
consider ABI surgery. Factors that increase the anesthetic risk (particularly cardiac arrest) among 
children undergoing surgery include: age<1 yr, obesity, other associated co-morbidities, ASA-PS 
>3, emergency surgery. Moreover, children undergoing elective surgery should be free of upper 
respiratory tract infection to reduce the risk of respiratory tract complication. Importantly, it is 
currently standard practice to undertake CI between 1 and 2 years of age. The risk for anesthetic-
related complications will be no different for this proposed group of children undergoing ABI 
surgery (58). While not specifically studied, the risk of major blood loss from ABI surgery is 
relatively small since tumor resection is not needed. If Chiari posterior fossa decompression 
surgery among children serves as a surrogate for blood loss risk in this population, a recent meta-
analysis suggested only 1 of 246 children experienced any bleeding related complication from 
this type of surgery (59). As stated below, children with any medical co-morbidities that place 
them at an increased risk for complication will be avoided in this trial.    
 Post-linguistic hearing loss (<18 yrs. of age) with both: 
o Loss or lack of benefit from appropriate CI without the possibility for revision 
or contralateral implantation. Examples might include: 
 Post-meningitis ossification 
 Bilateral temporal bone fractures with cochlear nerve avulsion 
 Failed revision CI without benefit 
o Previously developed open set speech perception and auditory-oral language 
skills 
 No medical contraindications 
 Willing to receive the appropriate meningitis vaccinations 
 No or limited cognitive/developmental delays which would be expected to interfere 
with the child’s ability to cooperate in testing and/or programming of the device, in 

Nucleus 24 ABI in Non-NFII Children 
 
13
developing speech and oral language, or which would make an implant and 
subsequent emphasis on aural/oral communication not in the child’s best interest 
 Strong family support including language proficiency of the parent(s) in the child’s 
primary mode of communication as well as written and spoken English. 
 Reasonable expectations from parents including a thorough understanding:  
o of potential benefits and limitations of ABI    
o of parental role in rehabilitation 
o that the child may not develop spoken language as a primary communication 
mode or even sufficient spoken language to make significant academic 
progress in an aural/oral environment 
 Involvement in an educational program that emphasizes development of auditory 
skills with or without the use of supplementary visual communication. 
 Able to comply with study requirements including travel to investigation sites.  
 Informed consent for the procedure from the child’s parents/legal guardian. 
Exclusion Criteria 
 Pre- or post-linguistic child currently making significant progress with CI 
This will be considered if a child is progressing along the expected speech reception hierarchy 
(SRI-Q) as detailed by Wang et al (50).  Even for the very young children (18 months of age 
with 6 months of use), nearly all children with a good auditory signal from their CI will have 
reached ceiling effects on the IT-MAIS and have pattern perception beyond chance using the 
ESP (50). Moreover, there will evidence of improvement in these metrics over time. 
 MRI evidence of one of the following:  
o normal cochlea and cochlear nerves or NFII 
o brainstem or cortical anomaly that makes implantation unfeasible 
 Clear surgical reason for poor CI performance that can be remediated with revision CI 
or contralateral surgery rather than ABI.  
 Intractable seizures or progressive, deteriorating neurological disorder  
 Unable to participate in behavioral testing and mapping with their CI. If this appears to 
be an age effect, ABI will be delayed until we can be assured that the child will be 
able to participate, as reliable objective measures of mapping are currently not 
available for mapping these devices.  
 Lack of potential for spoken language development. This will be considered the case 
when evidence of the following exist: 
o Severe psychomotor retardation, autism, cerebral palsy, or developmental 
delays beyond speech that would preclude usage of the device and oral 
educational development. Autism is a special case where there is the potential 
for delayed presentation. When early signs are considered present, our group 
routinely requests a comprehensive developmental assessment for further 
evaluation prior to considering routine evaluation. A specialized group is 
readily available at our institution for such an evaluation.  
 Unable to tolerate general anesthesia (cardiac, pulmonary, bleeding diathesis, etc.). 
 Need for brainstem irradiation 
 Unrealistic expectations on the part of the subject/family regarding the possible 

Nucleus 24 ABI in Non-NFII Children 
 
14
benefits, risks and limitations that are inherent to the procedure and prosthetic device. 
 Unwilling to sign the informed consent. 
 Unwilling to make necessary follow-up appointments. 
Device 
 
Subjects will be implanted with the commercially available Nucleus 24 Multichannel ABI 
and fitted with an approved Nucleus speech processor (Cochlear Corp, Sydney, AUS). 
 
Procedures 
 
All subjects will have the following study visits: Pre-operative visit(s), surgical 
implantation and hospitalization, post-operative follow-up, initial activation (4-6 weeks post-
implantation), 1, 3, 6, 12 18, 24, 30, 36 month visits. The following procedures will be carried 
out at the appropriate interval visits. 
 
 

Nucleus 24 ABI in Non-NFII Children 
 
15
Study Protocol Procedures Overview 
 
 
 
Screening 
 
Enrollment 
 
Preop 
 
OR 
 
Day 1 
Day 
2-5 
Initial 
Stimulation 
Month 
1 
Month 
3 
Month 
6 
Year 
1 
Every 
6 mos. 
Informed consent 
X 
 
X 
 
 
 
 
 
 
 
 
 
Medical 
Assessment 
 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
Imaging studies 
 
CT/MRI 
 
 
CT 
 
 
 
 
 
 
 
Electrophysiology 
 
 
 
X 
 
 
 
 
 
 
 
 
Sound Field 
Thresholds 
 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
Speech 
Perception 
Assessment 
 
X 
 
 
 
 
 
 
X 
X 
X 
X 
Speech/Language 
Assessment 
 
X 
 
 
 
 
 
 
X 
X 
X 
X 
Hospitalized 
 
 
 
X 
X 
X 
X 
 
 
 
 
 
Adverse Events 
Reporting 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Screening, Informed Consent, and Enrollment 
 
Patients will come from either the UNC Ear and Hearing and pediatric CI practices (>100 
new patients/yr.) or from outside the institution. It is anticipated that potential subjects from 
outside the institution will hear about the study through discussion among colleagues. The 
records of the UNC children currently in our program and known to have cochlear or cochlear 
nerve disorders that would make them potential candidates will be reviewed by the principal 
investigator to identify their potential candidacy. Children with such disorders are currently 
tracked as a part of the principal investigator’s secure patient list in WebCIS (Inner ear 
malformations list). During a routine patient visit, general interest in the study will be discussed 
in privacy. Should there be general interest, a detailed (~1 hr.) discussion will be scheduled to go 
through the entire protocol and consider informed consent. Both subjects that are interested and 
those uninterested in participation will be tracked and recorded. For those subjects that are not 
patients of the principal investigator, a knowledgeable individual will provide the subject with 
information and contact details of the investigator. The prospective subject can then initiate 
contact, if desired. There are no criteria that limit access among women or minorities. The 
requirement for participants to be primary English speaking families will limit access among 
non-English speaking individuals. This is a precondition because the investigators must be able 
to administer and judge speech and language test results that are English only in nature. This also 
allows for analysis among similar types of tests materials. Given the small number of 
participants, this is an unavoidable precondition.  
 
The Principal Investigator will inform the parent or guardian about all aspects of the study 
for implantation of the Nucleus 24 ABI including: study expectations and requirements, surgical 
procedure, and the postoperative evaluations and schedule. The risks of surgery and activation 
will be explained to the parent or guardian as outlined in the Institutional Review Board (IRB)-
approved Informed Consent Form. The potential limitations and advantages of implantation with 
the Nucleus 24 ABI shall also be explained.  
 
The parent or guardian will be given the opportunity to ask questions about the procedures, 
Informed Consent Forms and the study details prior to signing the Informed Consent Form. The 
parent or guardian will then be given a copy of the signed Informed Consent Form. For children 
old enough to participate in the process (7 yrs. and older) of informed consent, they will also be 

Nucleus 24 ABI in Non-NFII Children 
 
16
given an appropriate informed consent form to read and sign as deemed appropriate. Following 
informed consent, Inclusion/Exclusion criteria will be considered for the prospective subject. If 
the subject meets criteria, enrollment will be carried out. 
 
Medical History and Physical Examination 
 
This is a standard part of routine medical care. This will include a detailed evaluation as outlined 
by Buchman et al (49). Additional components unique to this evaluation will include: hearing 
history, CI history, medical/surgical history, vaccination history, social history, and physical 
examination. Review of appropriate audiometric and imaging studies will be conducted. The 
reasons for seeking these pieces of information are detailed below and listed in the Inclusion and 
Exclusion section above. 
Hearing history: Newborn infant hearing screening results, diagnostic auditory 
brainstem response testing results, as well as etiology, onset, duration, severity, and 
duration of profound hearing loss will be sought and recorded. The hearing history might 
identify issues relevant to understanding the etiology of the child’s hearing loss. As an 
example, children with evidence of passing the newborn infant screening and progressive 
hearing loss might have a degenerative neurological disorder rather than congenital hearing 
loss. This would be considered a contraindication to implantation (see exclusions). On the 
other hand, a pass on the newborn infant hearing exam using otoacoustic emissions and 
present cochlear microphonic on ABR would be consistent with cochlear nerve deficiency. 
Another important issue might be if a child had normal hearing and development prior to 
meningitis would be important for understanding the onset and duration of hearing loss.  
CI history: Date and hospital of implantation, ear implanted, device type, number of 
electrodes implanted in the cochlea and activated, duration of use, parental subjective 
assessment of performance and aversive reactions, date of explantation and reason (if 
applicable). Understanding these issues are extremely important for better assessing 
whether the reason for poor performance with a CI is related to the surgical procedure, a 
potential device abnormality, or the underlying disorder. Potentially, a child with a surgical 
reason for poor performance might be counseled to consider revision or contralateral CI 
rather than ABI. 
Medical/Surgical history: This will include a comprehensive review of medical 
conditions (cardiac, pulmonary, renal, neurological, metabolic, etc.) that are known to 
contraindicate major surgery as well as use of the implant (see Exclusions above). Previous 
surgical history including anesthetic history, details of CI surgery, and complications will 
be reviewed. A detailed review of systems will also be carried out and recorded. 
Vaccination history: The vaccination history will be carefully reviewed to assure 
compliance with the recommendations of the Centers for Disease Control (CDC) and the 
United States Food and Drug Administration (FDA) for individuals with CIs 
(http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5909a2.htm).  
Social history: A detailed social history will seek information regarding the parental 
support, educational and home environment. Specifically, issues related to parental ability 
to comply with the therapeutic and follow-up expectations of the protocol. This includes 
the parent’s commitment to developing audition skills for their child as a component of 
their communication strategy.  

Nucleus 24 ABI in Non-NFII Children 
 
17
Physical examination: A thorough physical examination with particular focus on the 
details of the head and neck, cardiac, pulmonary, and neurological systems will be carried 
out. CI sites as well as other surgical sites in the head and neck will be assessed. Ongoing 
otitis media will be identified and treated as needed. 
 
Imaging 
 
The imaging protocols and diagnostic criteria for the various inner ear malformations and 
CND are in active clinical use in our institution and will be carried out as described previously 
(27-30, 49). These will include both MRI and CT imaging. For children with a previous CI, the 
safety and need for MRI will be carefully considered. If previous MRI has been obtained and are 
of adequate quality, these will be sufficient. If the internal auditory canals (IACs) are very 
narrow on previous MRI or CT, MRI may also not be needed. If the diagnosis of CND is in 
question or the brain morphology is has not been adequately assessed, CI magnet removal will be 
considered prior to scanning. The imaging protocols include:  
 
MR Imaging Protocol. MR imaging is performed with a dedicated pediatric 
vestibulocochlear nerve (CNVIII) protocol, on either a 1.5T scanner (Sonata, Avanto, Vision, or 
Symphony; Siemens Medical Solutions, Malvern, Pennsylvania) or a 3T scanner (Magnetom 
Trio, Siemens Medical Solutions) by using a single- or 12-channel head coil. For young children, 
this may require general anesthesia. The protocol includes axial and sagittal unenhanced T1-
weighted images, axial T2-weighted images, and axial fluid-attenuated inversion recovery 
images through the entire brain, as well as high-resolution 3D CISS or RESTORE (Siemens 
Medical Solutions, Malvern, Pennsylvania) images through the temporal bones. Parameters for 
the CISS sequence varied by scanner (TR/TE/NEX, 5.42–12.25 ms/2.42–5.9 ms/1–2; FA, 50°–
80°; FOV, 120–180 mm; matrix size, 256), with resultant near-isotropic voxel sizes ranging from 
0.5 to 0.7 mm in length. The RESTORE sequence, which was performed only on the Sonata, was 
acquired with the following parameters: TR/TE/NEX, 1000 ms/136 ms/1; echo-train length, 21; 
FA, 180°; FOV, 140 mm; matrix size, 192, resulting in a voxel size of 0.7 mm. In most cases, 
patients were scanned under conscious sedation or general anesthesia. Total scanning time for 
each examination was approximately 20 minutes. The temporal bone sequences were 
reconstructed in the axial plane as well as in an oblique sagittal plane oriented perpendicular to 
the long axis of each IAC for viewing.  
 
CT imaging protocol. Temporal bone CT scans were performed on either a 16- or 64-slice 
CT scanner (Sensation 16 or Sensation 64; Siemens Medical Solutions). Contiguous direct 
sequential axial and coronal images (120 kVp, 200 mAs) are acquired through the temporal 
bones using a collimation of 0.6 or 0.75 mm.  
 
All MRI and CT images will be reviewed on a clinical picture archiving and 
communication system (IMPAX 5.0; AGFA, Ridgefield Park, NJ, USA). All quantitative 
measurements are made using the standard ruler tool included in our picture archiving and 
communication system software package.  
 
Audiological Assessment 
  

Nucleus 24 ABI in Non-NFII Children 
 
18
Pre- and Post-operative Behavioral audiometry and speech perception testing. The 
standard clinical CI speech perception and speech and language test battery will be used.  This 
testing is in common use every day in our clinics. Tests will be presented in a sound-controlled 
sound booth using monitored live voice (50 dB HL) in the auditory only condition or recorded 
materials (60 dB SPL). These tests include:  
 
 Detection audiogram, aided and unaided individual ears 
 IT-MAIS or MAIS 
 LING 6 sound test 
 ESP Low Verbal or Standard- MLV @ 50dB HL 
 PB-k words and phonemes- MLV @ 50dB HL 
 MLNT- recorded @ 60dB SPL                                  If >50% then 
 LNT- recorded @ 60dB SPL  
                        If >80%, then 
 CNC- 50 words @ 60dB SPL 
 HINT-C- 2 lists of 10 @ 60dB SPL 
 
Standard audiometric techniques will be performed for measuring sensitivity to sound with 
the ABI activated. Visual reinforcement audiometry will be performed to measure sound field 
thresholds up until the child is 30 to 36 months of age. Conditioned play audiometry will be 
performed when the child is approximately 30 to 36 months of age and older. Stimuli will be 
delivered via loudspeaker in the auditory only mode consisting of live-voice speech and warbled 
tones or narrow-band noise for 250, 500, 1000, 2000, 4000, and 6000 Hz. These tests will be 
used to document profound hearing loss preoperatively as well as the level of sound detection 
using the device in the post-operative period.  
 
The following speech perception measures are routinely used with CI recipients and 
represent a hierarchy in both the child's required response and the difficulty of test 
material.  When a child is not able to participate in structured testing for any reason including 
age, attention, or level of auditory development, then a parental questionnaire is used (IT-MAIS 
or MAIS).  The earliest developmental response format is detection and imitation (LING 6-sound 
test), followed by a small (4 items) closed-set format (ESP-low-verbal) and then a larger (12 
items) closed-set format (ESP standard).  Open set speech recognition follows (PB-k, MLNT, 
LNT).   Each child will be assessed starting with the lowest level of the battery at each 
assessment interval until a 100% score is achieved at 2 consecutive test intervals.  Criteria for 
moving on to the next test are based on the child's developmental (behavioral and auditory) 
skills, not chronological or hearing age. 
 
Meaningful Auditory Integration of Sound (MAIS) and Infant-Toddler Meaningful Auditory 
Integration of Sound (IT-MAIS) (51, 52). The MAIS is a 10-item parent-report scale 
designed to evaluate developing auditory behavior in children ages 4 years and older. Parents 
rate how often their child engages in specific behaviors with regard to their child’s bonding 
with the sensory device, auditory awareness, and the ability to derive meaning from sound. 
The IT-MAIS was developed for children younger than 4 years. While it shares the majority 
of questions with the MAIS, the IT-MAIS additionally explores vocal behavior of infants 
with their sensory device. The MAIS probes ten questions in a structured parent interview, 

Nucleus 24 ABI in Non-NFII Children 
 
19
assessing the child’s bonding with the sensory device, auditory awareness, and ability to 
derive meaning from sound in everyday situations.  
 
Ling Six Sound Test (Ling, 2002/2003). The Ling Six Sound Test samples the child’s ability 
to detect and identify speech sounds representative of the speech frequency spectrum (ah, oo, 
ee, sh, s, m). The test is administered live-voice.  
 
Early Speech Perception (ESP) Test (53). The ESP is designed to assess pattern perception 
(differentiation of syllable number and stress pattern), spondaic word identification (two 
syllable word with equal stress on each syllable), and monosyllabic word identification in a 
closed-set.  Attainment of a criterion level is required to pass each sub-test. This test is 
generally introduced when the child is 2 years of age or when he or she is able to choose 
between two alternatives. There is a standard version and a low-verbal version. Stimuli for 
both versions are typically presented live voice. 
Multisyllabic/Lexical Neighborhood Test (MLNT/LNT) (54). The MLNT and LNT are 
open-set tests that explore the lexical properties of spoken word recognition. The words are 
divided into easy and hard lexical categories based on word frequency and phonetic 
similarity. The stimuli consist of multisyllabic words in the MLNT and monosyllabic words 
in the LNT.  
 
Phonetically Balanced Kindergarten Word Test (PB-k) (55). The PB-k is an open-set test of 
50 words that are meant to represent the distribution of phonemes in English using 
kindergarten level vocabulary.  The child repeats the word and his responses are scored for 
the correct word and number of phonemes repeated.  This will be presented in a monitored 
live voice mode. 
 
Consonant- Nucleus-Consonant Word Test (CNC) (56).  The CNC is an open-set test which 
includes 10 lists of 50 words recorded by a male speaker. This test was developed to provide 
lists of monosyllabic words with equal phonemic distribution across lists with each list 
exhibiting approximately the same phonemic distribution as the English language.  
 
Children’s Hearing in Noise Test (HINT). The HINT test is made up of 12 lists of 10 
sentences; each sentence is 5 to 7 words in length.  The child repeats as much of the sentence 
as possible and points are given for key words repeated.  Noise may be added to this test to 
increase its difficulty. 
 
Speech and Language Assessment  
 
Communication mode and educational setting are identified and recorded by the managing 
audiologist and/or speech pathologist at our institution. The following tests will be administered 
in their standardized forms. The raw scores will be used to compare children to their 
chronologically aged peers with typical hearing to determine standard scores by following testing 
protocols. Results will be discussed using comparative measures to the subject's hearing age with 
the ABI as well. Our protocol for speech-language evaluations are well established for our 
population with CIs despite very little time with usable hearing. This same protocol will be used 
to effectively assess children's spoken language development with an ABI. There are at least 2 

Nucleus 24 ABI in Non-NFII Children 
 
20
dedicated speech pathologists on the pediatric CI team with extensive experience using these 
measures in children within the proposed age range. The standard clinical test battery includes: 
 
MacArthur-Bates Communicative Development Inventories (CDIs) (57). CDIs are parent-
report instruments designed to evaluate early receptive and expressive language skills in 
children. The CDI/Words and Gestures assess vocabulary comprehension, production and the 
use of gestures typically used by children in the 8-to-18 month age range. The CDI/Words 
and Sentences extend the list of vocabulary words and probe a number of aspects of 
grammatical development typically acquired by 30 months of age.  
 
Pre-School Language Scale, Fourth Edition (PLS-5) (Zimmerman, Steiner, & Pond, 2010).  
The PLS-5 is a standardized language test designed for infants and young children.  The 
Auditory Comprehension subscale targets skills known to precede language development, 
including: attention to speakers, appropriate object play, basic vocabulary, concepts, 
grammatical markers, and complex sentences.  The Expressive Communication subscale 
assesses vocal development, social communication, naming of common objects, 
phonological awareness, sequencing skills, as well as use of concepts, prepositions, 
grammatical markers, and varying sentence structures.   
 
The Oral and Written Language Scales (OWLS) (Elizabeth Carrow-Woolfolk) The OWLS 
assesses the comprehension and expression of language of children 3 to 21 years of 
age.  This test examines an individual’s ability to understand and produce connected 
language looking specifically at vocabulary, grammar, pragmatic function and higher order 
structures of language. 
 
Goldman-Fristoe Test of Articulation. (Goldman-Fristoe, 1986).This test assesses a child's 
articulation ability by sampling both spontaneous and imitative speech production. Pictures 
and verbal cues are used to elicit single word answers that demonstrate common speech 
sounds. The Goldman-Fristoe measures the articulation of speech sounds and identifies and 
describes the types of articulation errors produced by the child. 
 
Surgery  
 
Nucleus Multichannel ABI will be placed using the retrosigmoid craniotomy on the side 
opposite the child’s previous CI (when present) and assuming there are no obvious 
contraindications. This approach provides direct access to the lateral recess of the 4th ventricle 
and region of the cochlear nucleus. This approach has previously been documented to be safe in 
the literature for this use (48) and has been used extensively in adults and children at our 
institution for other causes. Our team has extensive experience with cerebellopontine angle 
surgery (i.e. the region of interest). In 2009-2011, we carried out 71 cerebellopontine angle 
craniotomies for acoustic neuromas (16 retrosigmoid). In that time period, there were a total of 
120 retrosigmoid craniotomies in adults and 42 in children. We have also carried out the only 
retrosigmoid approach for ABI placement in an adult patient without NFII in the United States to 
date (see images and description below). 
 
Surgery is carried out under general endotracheal anesthesia, without paralytic agents, and 
is administered by a pediatric anesthesiologist in a children’s hospital operating room. The child 

Nucleus 24 ABI in Non-NFII Children 
 
21
will have 2 large bore intravenous catheters placed. Following induction, the child will be 
maintained under normotensive anesthesia using a combination of inhalational and intravenous 
agents. The auditory monitoring montage will be placed as described below. Cranial nerve 
electromyography monitoring will consist of bipolar, needle electrodes placed in the ipsilateral 
facial muscles (orbicularis oris and oculi-CN VII), soft palate (CN IX-X), and trapezius (CN XI). 
Appropriate monopolar needle electrodes will serve as ground and stimulating electrodes and 
will be placed in the pre-sternal subcutaneous skin. The NIM-Response® 3.0 (Medtronic, 
Minneapolis, MN) nerve integrity monitor will be used to continuously monitor EMG activity 
under both spontaneous conditions as well as under evoked testing.  
 
The patient will be positioned in an age appropriate head holder in a modified lateral 
position to expose the suboccipital cranial region. An appropriate location for the receiver 
stimulator will be identified based on the device templates and marked with injection of 
methylene blue on to the skull in a routine fashion. A post-auricular incision will be marked and 
infiltrated with 1 lidcaine and 1:100,000 epinephrine solution. Monopolar cautery will be 
avoided to protect the child’s previous CI. Following skin flap creation, the region of the 
retrosigmoid craniotomy will be exposed based on standard surgical landmarks (asterion, inion). 
A standard, retrosigmoid craniotomy (~2.5 x 2.5 cm) will be created, exposed mastoid air cells 
occluded with bone wax and the suboccipital dura exposed.  
 
Dural incisions will open the posterior cranial fossa and using the operating microscope, 
CSF is drained from cisterna magna and the lateral cerebellopontine angle cistern with gentle 
retraction. The posterior-ventral and dorsal cochlear nucleus is the most accessible portion of the 
nucleus complex for electrical stimulation. These structures are located on the anterior surface of 
the lateral recess of the 4th ventricle and can be visualized. After cerebellar relaxation, the lower 
cranial nerves are identified and the IX cranial nerve and choroid plexus emanating from the 
Foramen of Luschka will be viewed with gentle retraction of the cerebellar flocculus. The facial 
nerve, ventral to the lateral recess and cochleovestibular nerve and/or its remnant as well as the 
lower cranial nerves exiting inferiorly are identified and confirmed with stimulation. Opening the 
recess arachnoid may reveal the choroid plexus and can release CSF to aid in identification. 
Upon opening the recess, the cochlear nucleus prominence is evident on anterior wall.  
 
The receiver-stimulator of the Nucleus 24 Multichannel ABI will be seated in a depression 
on an appropriate site on the skull, based on methylene blue markings placed prior to incision. 
The receiver-stimulator will be immobilized with periosteal sutures and a trough for electrode 
immobilization created if skull thickness permits. The array will be advanced in to the recess 
with the array facing the nuclear prominence as shown in Figure 1 below and Teflon® felt used 
to secure the array. The separate ground, ball electrode will be advanced under the temporalis 
muscle periosteum in a standard fashion. Electrophysiologic testing will then commence as 
described below. If testing confirms responses on a number of electrodes, closure will commence. 
If testing does not reveal responses, exploration will be undertaken to again confirm location.   
 
 

Nucleus 24 ABI in Non-NFII Children 
 
22
 
 
Figure 1. Intraoperative image (left) from an adult patient with a history of post-meningitis hearing loss and severe 
cochlear ossification that failed CI and underwent left retrosigmoid craniotomy with insertion of a Nucleus 24 
Multichannel ABI at UNC-Chapel Hill in 7/2007.  Responses recorded from implant stimulation are shown on the 
right. The left image shows the ABI array in place (), normal choroid plexus (), 8th cranial nerves behind the 
electrode wire, and 9th nerve () entering the lateral recess of the 4th ventricle. The implant array is seen exiting the 
recess and Teflon® felt (✖) is seen securing the position of the electrode array. 
 
 
 
 
Figure 2. Postoperative CT image of the patient above showing Nucleus 24 Multichannel ABI well positioned in the 
lateral recess of the 4th ventricle.   
 
Intraoperative Electrophysiology Testing  
 
Intraoperative electrically-evoked auditory brainstem response (EABR) testing is 
undertaken to provide electrophysiological information concerning device placement and 
functionality. The primary electrode montage for EABR testing is midline, with the non-inverting 
electrode at Cz (vertex), the inverting electrode at C7 (cervical vertebra 7), and the ground 
electrode at the nape-of-neck (hairline). A discretionary duplicate set of electrodes can also be 
placed with the non-inverting electrode at Fz (high forehead), the inverting electrode anterior to 
the tragus on the ear contralateral to the surgical side, and the ground electrode at Fpz (mid-
eyebrows). In all cases, electrodes are 15-20 mm subdermal needle electrodes sutured in place or 

Nucleus 24 ABI in Non-NFII Children 
 
23
otherwise fixed with tape. All electrode leads are labeled, braided together, and positioned away 
from the surgical field with their terminals accessible. Electrode placement necessarily occurs 
during the preparation of the patient for surgery, and it is recommended that the impedances of 
the electrodes be measured at the time of placement to ensure optimum connectivity. 
 
Following device placement, a series of bipolar stimulations are undertaken in an effort to 
elicit auditory-evoked responses. In general, initial electrode pairings for bipolar stimulation are 
transverse across the length of the device (see schematic of electrode pad in Figure 1b), with 
subsequent pairings honing in on more spatially localized stimulation, as dictated by the pattern 
of results and available testing time. The objective is to grossly map out the regions of the 
electrode pad that are conducive to auditory stimulation. This mapping allows interpretation in 
terms of placement/orientation of the electrode pad relative to the surface of the cochlear nucleus, 
and may guide device re-positioning decisions. 
 
Stimulation parameters for this mapping process are optimized for auditory-evoked 
responses. Typical parameters include biphasic pulses (150 µSec/phase) presented at a rate of 35 
Hz at a level of at least 150 CUs. When responses are observed, pulse polarity should be reversed 
to confirm the neural basis (see sample traces in Figure 1b). Stimulation is provided through the 
NRT Nuclear Response Telemetry system from Cochlear Ltd. using the Portable Programming 
System (PPS). For this testing, the head coil is placed within a sterile sheath and positioned over 
the receiving antenna of the implant. The PPS is connected to a Sprint speech processor that is 
stimulated by the Nucleus programming software NRT 3.1. The PPS also provides a TTL trigger 
to synchronize the EABR recording system. These systems are approved for use as a part of the 
Nucleus 24 ABI System. 
 
The recording parameters are optimized for EABR recording. Typical parameters include 
wideband recording filters (e.g., 100 – 5000 Hz), 10-mSec recording window, amplifier gain of 
X100,000 with artifact rejection turned off. Number of averages is dictated by the quality of the 
response and is typically set to 500-1000.  
 
Surgical Closure 
 
Once the array is optimally placed, the dura will be closed with interrupted sutures.  As the 
closure cannot be completely watertight owing to the cable from the array, abdominal fat may be 
harvested and used to create a watertight closure.  The bone flap if present can be replaced with 
titanium mesh and screws or a complete mesh cranioplasty may be placed. 
 
Postoperative Care  
 
Following surgery, the child will be admitted to a specialized pediatric intensive care unit 
(PICU) in the North Carolina Children’s Hospital. The unit is staffed full time by pediatric 
intensive care specialists with expertise and experience in pediatric neuro-intensive care. The 
child is monitored continuously using both invasive and non-invasive methods as needed. These 
may include an arterial line, central venous pressure (CVP) line, urinary catheter, blood pressure, 
pulse oximetry, EKG, and continuous nursing observation. It is anticipated that the child’s 
endotracheal tube will be removed early in the postoperative period, either in the operating room 
or while in the PICU. Ventilator support as well as pain control and adequacy of sedation will be 

Nucleus 24 ABI in Non-NFII Children 
 
24
closely monitored while an endotracheal tube is indwelling. Intravenous antibiotics will be 
administered for a no more than 24 hours following surgery in accordance with current 
recommendations from the American Association of Neurological Surgeons (AANS) and the 
American College of Surgeons (ACS).  If the patient is allergic to penicillin or the 
cephalosporins, vancomycin will be administered intravenously for 24 hours. The pharmacy will 
be consulted for specific dosing based on the patient’s weight. Corticosteroids will be 
administered for approximately 2 weeks or less following the surgery to minimize any brains 
swelling. Pain medication will be given prophylactically early on and as needed in the post-
operative period. A CT scan will be obtained on the first postoperative night to evaluate for brain 
swelling and electrode array location (Figure 2 example). The patient in mobilized, and diet is 
advanced on the first postoperative day as tolerated. Intravenous fluids are weaned as oral intake 
increases. 
 
The child is discharged from the PICU to a standard pediatric surgical floor no sooner than 
postoperative day 1 (day after surgery) or later as medically indicated. De-intensification 
includes removal of the urinary catheter, and discontinuation of continuous EKG and oximetry 
monitoring. On day 3 following surgery, the incision will be examined for CSF leakage. In the 
absence of a leak, the child will be discharged home with instructions for the parents to follow-
up in one week as an outpatient. Appropriate phone numbers are provided for the clinics, 
hospital, and emergency department as well as details that should prompt the family to return to 
the hospital. These would include: increasing pain, swelling, nausea, vomiting, fever, shortness 
of breath, rapid breathing, changes in mental status, or anything that concerns the parents.  
 
Should the child develop CSF leakage from the wound, over-sewing will be carried out as a 
sterile procedure. Should the child develop rhinorrhea, surgical re-exploration of the wound or 
lumbar subarachnoid drainage will be undertaken depending on the age and cooperativeness of 
the child and the presence and violation of the mastoid air cells that were observed at the time of 
surgery. 
 
Initial Activation and Follow Up Testing 
 
At the initial stimulation and at subsequent device programming sessions, a combination 
of objective data and behavioral methods will be used to program the speech processors.  Data 
gathered from intra-operative electrophysiological testing that identified electrodes with optimal 
responses to stimulation would be selected for inclusion in the speech processor program. As 
with the initial stimulation of CIs in young children, behavioral observation and conditioned 
behavioral audiometry techniques will be used to determine electrical thresholds and comfortable 
listening levels. The initial stimulation will take place in the ENT clinic with pediatric anesthesia 
support. Starting with electrode pairs that elicited the best, evoked responses in the OR, 
stimulation will commence in a conservative fashion, using an ascending approach, until a 
behavioral response is observed.  It will be documented when stimulation awareness is observed. 
Depending on the child’s level of cooperation, conditioning of that response will ensue. During 
the initial stimulation and subsequent programming sessions, the child will be trained to 
participate in device setting.  If stimulation levels result in visible or aversive responses (facial 
contraction, throat tickle, cough, shoulder activation, extremity sensations) higher stimulation 
levels will not be attempted. Although young children who have no auditory experience are 
limited in their ability to provide feedback about stimulation, our team of pediatric CI 

Nucleus 24 ABI in Non-NFII Children 
 
25
audiologists has extensive experience in monitoring behaviors and interpreting responses to 
auditory electrical stimulation from children as young as 9 months of age on a routine basis.  It is 
anticipated that the programming of the speech processor for the ABI will be similar in practice 
to programming CIs using a progressive mapping approach which includes making incremental 
changes to current levels over time, allowing for comfortable adaptation to sound.  Only 
programs that have been stimulated in the clinic will be programmed to the user speech 
processor. The children will be seen at the designated follow up appointments for device 
programming at 4 weeks post initial stimulation and at 3, 6, 12, 18, 24, 30, 36 months for 
mapping and assessment including behavioral audiometry and speech perception testing. A 
language assessment will be repeated at 6-month intervals. 
 
Data and Analysis 
 
A single-subject research design was chosen (in which each subject serves as their own 
control) in order to accommodate for the heterogeneity that is well known to characterize 
auditory prosthesis research. Post-operative evaluations will be conducted at the initial activation 
and at 1, 3, 6, 12, 18, 24, 30, and 36-month intervals post-activation. Blinding or masking 
procedures are not included in the design, as the presence/absence of a brainstem implant cannot 
be easily concealed from the device recipients and/or clinical investigators. 
 
Data will include demographics, frequency of both major and minor complications as well 
as audiometric and speech and language data. The summary statistics will be reported on the 
various categorical (gender and complications) and continuous (age, audiological and speech 
perception, production and language scores) variables. 
 
Baseline audiological and speech perception, production and language measures taken 
prior to ABI surgery will be compared to scores at each follow up interval within each subject. 
For subjects with no response on behavioral testing, a maximum score of 120 dB HL will be 
assigned at the test frequency as this represents maximum stimulus levels of the equipment. Pure 
tone average (PTA) is calculated using the thresholds from 500, 1,000, and 2,000 Hz. When 
speech perception testing is limited by short duration experience or young age, inattention, or the 
presence of significant comorbidities, these reasons will be recorded. When inability to complete 
the test is evident despite significant implant experience, the patient is assigned the value for 
chance correct responses for the appropriate test (i.e., 0% for open-set tests or 33% for ESP 
pattern-[P] perception tests). When a child advances out of a particular measure because of 
ceiling effects, then the next measure will be undertaken. For children able to perform a given 
speech perception measure(s) prior to ABI surgery, that measure(s) will be repeated at the initial 
post-operative visits to insure the same test comparisons exist. It will be assumed that children 
that are unable to perform closed set testing will not be able to perform open set testing at a 
given visit. Thus, scores on these tests will be assigned the value of “unable to test”.  
Change values for each of the variables will be calculated by subtracting off baseline 
values when available. The mean percent change at the various intervals for each variable can be 
averaged (+/- SD) across the subjects. Comparison to baseline measures for significance testing 
will be made with 95% confidence intervals when possible. The chance that this is not possible 
exists because of the broad variation in ages and possible achievements with the device.  

Nucleus 24 ABI in Non-NFII Children 
 
26
For speech perception, there is a developmental hierarchy that is required to evaluate the 
emergence of this skill over time. This will be tracked and plotted on a graph against similar 
children with normal hearing as well as those fitted with CIs with and without malformations for 
comparison (30, 50). This modified cumulative speech perception index in quiet (SRI-Q) will be 
created after Wang et al. (50) and Buchman et al (30) in an effort to simultaneously display the 
data from all tests in the speech recognition hierarchy as a function of time. ESP-P is considered 
easier than ESP-monosyllabic (M) words. CNC word scores then follow PB-k word scores. The 
measured percentage score for each test (0%–100% correct) is then hierarchically ranked and 
stacked in 100-point increments. These results are controlled for duration of device usage and 
age at implantation. Speech production and language data are reported as age-normed values and 
will be compared to children of a similar age with normal hearing as well as those using CIs. 
 
It is anticipated that this pilot study will be used to demonstrate safety and give some idea 
regarding efficacy. However, a larger scale clinical trial will be needed beyond the pilot study to 
demonstrate surgical safety on a broader scale (across surgeons and institutions) and the utility of 
the device for the intended auditory benefits. Ten subjects should be a sufficient sample size to 
demonstrate safety. If the European data is correct regarding complication rates in children, a 
single CSF leak might occur in one subject and non-auditory side effects can be expected to 
occur in roughly 20% of children or 2 subjects in this study. This number seems to be a 
conservative and reasonably small number to demonstrate these effects. Non-auditory 
stimulation is not serious and can be programmed around with simple changes in device 
programming during activation. For speech perception and production, the within subject design 
should allow us to see some benefit from the device if effective. Since the children are deaf, any 
development of significant open or closed set perception (beyond patter perception) would be 
attributable to the device. Similarly for language outcomes although these will take longer time 
to develop. Thus, the safety numbers are the drivers in powering this study. 
 
The data will be recorded in patient-specific binders on a case-by-case basis after each 
subject encounter. All data will be entered in to the secure, File Maker Pro, customized database 
for CI research housed in the Department of Otolaryngology-Head and Neck Surgery that is 
currently in use. The lead investigator will cross check the data prior to approval for review. The 
data will be exported by desired fields to an Excel spreadsheet (Microsoft) for further analysis. 
Statistics will be carried out using SPSS software. If needed, statistical consultation will be 
sought at the University TRACS or Odum Institute. 
 
Study Endpoints 
 
 
Study endpoints are based on the 3 specific aims. For safety, this will be determined on a 
case-by-case basis and any adverse events will be reviewed with the IRB and the data monitoring 
board (2 individuals appointed). Should the adverse events be deemed unacceptable to the 
investigators, the IRB, or the monitoring board, this would be sufficient terms for study 
discontinuation. Three years of follow up was chosen to provide adequate time for the 
emergence of open-set speech perception abilities in the pre-lingual cohort of children. In studies 
of prelinguistic children undergoing CI, at least 2 years of follow-up is needed to demonstrate 
emergence of these skills (23). If no open set perception is demonstrated at 3 years, this seems to 
be good evidence for a lack of benefit on this measure. In general, speech and language measures 
should track speech perception abilities. While the full emergence of these skills can take 

Nucleus 24 ABI in Non-NFII Children 
 
27
somewhat longer to develop, it is anticipated that early emergence will be evident if speech 
perception is developing. While not anticipated, a clear lack of benefit from the device (such as 
no sound awareness) among multiple subjects would also be consideration for stopping the study. 
Study recruitment is expected to be slow at 1-3/year. This will not stop the study. 
 
Human subject protection measures 
 
Risks and measures to minimize risk. There is limited psychological, social, legal and 
economical risk to patients for participating in this study. The potential for a confidentiality 
breach is rare. All children and their parents will be treated confidentially according to HIPAA 
and its requirements. All discussion of the results of the intervention for the purposes of results 
reporting will be made anonymously.  
The physical risks include medication side effects, pain, discomfort, or injury from 
participation. The potential risks from participation are likely (10-25%) and dependent on the 
consequences in question. The potential complications have been detailed above.  
Complications related directly to the ABI have been unusual. Toh and Luxford indicated 
the most common complications in ABI surgery appear to be cerebrospinal fluid (CSF) leak, 
electrode migration, and non-auditory side effects during stimulation. There have been no 
fatalities related directly to the placement of the ABI. Rather, mortality has occurred in patients 
treated for brain tumors from NFII in the same location where surgery was prolonged and the 
patients developed pulmonary embolism post-operatively. Electrode migration appears to be a 
complication that occurs in patients undergoing ABI in the setting of tumor removal where 
distorted brainstem anatomy results in a shallow or deformed lateral recess. Following surgery, 
brain re-expansion might displace the electrode. 
 
CSF leaks are an expected risk from any surgery where CSF cisterns are entered.   Otto et 
al reported 2 CSF leaks among 61 patients following translabyrinthine tumor removal and ABI 
placement that resolved with either a pressure dressing or a temporary lumbar subarachnoid 
drain (47). Grayelli et al. also reported 2 cases of CSF leaks after 31 ABI surgeries and 
Sennaroglu et al. reported one case of a CSF leak in a child who underwent retrosigmoid ABI 
placement that resolved with would exploration and repair of the air cell opening (42, 43). 
 
Colletti et al reported on 114 ABI operations performed through the retrosigmoid approach 
in Verona from 1997 to 2008 in 83 adults and 31 children (48). Thirty-six had NFII (34 adults 
and 2 children), and 78 (49 adults and 29 children) had cochlear or cochlear nerve disorders 
unrelated to NFII. The table on page 7 details the complications from this study. There was a 
statistically lower risk for complications among the patients without NFII, presumably because 
there was no need for tumor removal prior to device placement. Importantly, there was 1 major 
complication in a child implanted in Manchester, England. That child developed a cerebellar 
contusion and swelling requiring a return to the operating room for evacuation. This child 
recovered without neurological sequelae. 
 
Other complications in children included wound seroma (n=4) that were managed with 
aspiration and bandage, minor wound erythema treated with antibiotics alone, and transient 
balance problems that resolved without treatment. 

Nucleus 24 ABI in Non-NFII Children 
 
28
 
Non-auditory side effects are a relatively common occurrence from ABI stimulation and 
are usually related to activation of the neural tissue in the region of the implant. Toh and Luxford 
reported non-auditory side effects in 42% of multichannel ABI users following tumor removal in 
NFII patients (44). Colletti et al (48) reported ipsilateral body tingle was observed in 2 children 
(6.9%), facial nerve stimulation in 2 (6.9 %), dizziness in 1 (3.4%), headache in 1 (3.4%), and 
throat tingle/tickle in 1 (3.4%) child. In adults, ipsilateral body tingle was observed in 10 subjects 
(8.7%: 7 NFII and 3 non-tumor), facial nerve stimulation in 6 (5.2%: 4 NFII and 2 non-tumor), 
dizziness in 15 (19%: 9 NFII and 6 non-tumor), headache in 5 (6 %: 3 NFII and 2 non-tumor), 
and throat tingle/tickle in 8 (9.6%: 5 NFII and 3 non-tumor). These side effects are all alleviated 
with selective electrode deactivation. Re-activation of the offending electrode over time usually 
resolved the issue. 
 
In summary, discomfort from non-auditory stimulation seems likely although in children 
the risk appears to be less than 20%. The other complications are very unlikely or infrequent. 
Pain following surgery is probably an expected occurrence that will be managed with pain 
medication. The risk of long-term headache seems rare. 
 
Data and safety monitoring. Subjects will be monitored on a case-by-case basis for ongoing 
or unanticipated medical complications. Adverse events will be tracked on a case-by-case basis 
and recorded in study binders at the time of occurrence and followed up at resolution. Any 
adverse events will be reported to the IRB. Should there be concern for the safety of the subjects 
because of their participation in the study by the investigators or the IRB, the study would be 
halted at least temporarily and a detailed discussion with the investigators and the IRB would be 
undertaken to evaluate the viability of the study. Two chosen experts in the field will also review 
serious adverse events as external reviewers.  
 Thomas J. Balkany, MD Professor and Chairman Emeritus, Department of Otolaryngology-
Head & Neck Surgery, University of Miami, Miami, FL. Email: tbalkany@med.miami.edu 
 J. Thomas Roland, MD Professor and Chairman, Department of Otolaryngology-Head & 
Neck Surgery, New York University, New York, NY. Email: John.Roland@nyumc.org 
Unanticipated adverse device effect (UADE) is defined as any serious adverse effect on 
health or safety or any life-threatening problem or death caused by, or associated with, a device, 
if that effect, problem, or death that was not previously identified in nature, severity, or degree of 
incidence in the literature or investigational plan.  It can also include any other unanticipated 
serious problem associated with a device that relates to the rights, safety, or welfare of subjects. 
  
As required by 21CFR 812.150, the sponsor will report any UADE to the FDA within 10 
days of learning of the event, and to the local IRB per institutional guidelines. 
 
Participants or their families can withdraw from the study at any time by notifying the 
primary investigator.  If the investigator identifies the need to withdraw a participant from the 
study for any reason, this will be discussed in person during a scheduled evaluation. The subject 
will still receive ongoing care irrespective of their participation in the study. Should the subject 
not be able to use their device, or develops complications related to participation in the study, 

Nucleus 24 ABI in Non-NFII Children 
 
29
their participation in the study will end when their study related morbidity has resolved or is no 
longer active. Again, this will not affect the ongoing medical care for the subject.  
 
Ongoing morbidity and adverse events deemed unacceptable to the investigators, the IRB, 
or the external reviewers would be sufficient terms for study discontinuation. Moreover, a lack of 
benefit from the device among multiple subjects would also be consideration for stopping the 
study. Study recruitment is expected to be slow at 1-3/year. This will not stop the study. 
 
 
Confidentiality of the data. Subjects will be assigned a specific, anonymous participation 
code that will be associated with their particular data file. Database entry will be by participation 
code only. All personal identifiers will be kept in a separate, secure data file that will be 
password protected and not associated with the primary data. Only the principal investigator will 
have access to these codes. 
 
Patient specific binders will be kept in a single location in a locked cabinet. Individual data 
collection sheets will be coded and placed in the patient-specific binders immediately after 
coding. For analysis, the data will not include specific personally identifiable names, dates of 
birth, medical record numbers, etc. (PHI). 
 
Given the pilot nature of the project and the relatively small number of subjects and 
anticipated occurrences, deductive disclosure is possible if a subject experiences a unique 
adverse event that other investigators are aware of. There will be limited to no potential for those 
outside the study to deduce the identity of the subject unless they were somehow associated with 
them personally. Data will not be shared outside the primary investigative team except during 
reporting of results anonymously. 
 
Data will be stored in a locked file cabinet until the time the study is closed and then it will 
be shredded and destroyed in a HIPAA compliant manner.  There are no human or biological 
specimens.   
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov.  This 
Web site will not include information that can identify research subjects.   
 
Institutional Review Board 
University of North Carolina Biomedical Institutional Review Board (IRB) 
Co-Chairs: Ina Friedman, J. Herbert Patterson, David Weber, J. Douglas Mann,  
Address: Medical School Building 52, University of North Carolina - Chapel Hill 
Mason Farm Road, CB #7097 
Chapel Hill, NC 27599-7097 
(919) 966-3113 
 
 
 
 
Attached 

Nucleus 24 ABI in Non-NFII Children 
 
30
 Informed Consent and Assents 
 HIPAA Authorizations 
 PMA Letter 
 Device Description 
 
 
 
 
 

Nucleus 24 ABI in Non-NFII Children 
 
31
REFERENCES 
   
1. Stone HE. Adjustment to post-lingual hearing loss. In: Kyle JG, ed. Adjustment to acquired 
hearing loss. Bristol, England: Centre for Deaf Studies; 1987. 
2. National Institutes of Health. Early identification of hearing impairment in infants and young 
children. Bethesda, MD: National Institutes of Health; 1993:1-24. NIH consensus statement 
11(1). 
3. Gilmore SI. Social and vocational acceptability of esophageal speakers compared to normal 
speakers. Journal of Hearing and Speech Research. 1974; 17:599-607. 
4. Appollonio A, Carabellese C, Frattola L, Trabucchi M. Effects of sensory aids on the quality 
of life and mortality of elderly people: A multivariate analysis. Age Aging. 1996; 25:89-96. 
5. Barnett S, Frank P. Deafness and mortality: Analyses of linked data from the National Health 
Interview Survey and National Death Index. Public Health Rep. 1999; 114:330-336. 
6. Foster S. Educational programmes for deaf students: An inside perspective on policy and 
practice. In Barton L, ed. Integration: Myth or reality? Bristol, England: Falmer Press; 
1989:57-82. 
7. Garland MH. Depression and dementia. Hospital Update. 1978; 313-319. 
8. Herbst KG, Humphrey C. Hearing impairment and mental state in the elderly living at home. 
BMJ. 1980; 281:903-905. 
9. Holt JA. Stanford Achievement Test, 8th edition: Reading comprehension subgroup results. 
Am Ann Deaf. 1993; 138:172-175. 
10. Jarvelin MR, Torkko EM, Sorri MJ, Rantakallio PT. Effect of hearing impairment on 
educational outcomes and employment up to the age of 25 years in northern Finland. Br J 
Audiol. 1997; 31:165-175. 
11. Johnson VA. Factors impacting the job retention and advancement of workers who are deaf. 
The Volta Review. 1993; 95:341-356. 
12. Kyle JG, Allsop L. Deaf people and the community: Final report to the Nuffield Foundation. 
Bristol, England: School of Education Research Unit, University of Bristol; 1982. 
13. MacLeod-Gallinger J. The career status of deaf women. Am Ann Deaf. 1990; 137:315-325. 
14. Walter GG, MacLeod-Gallinger J. Current employment classifications, demands and 
opportunities. Paper presented at the National Conference on the Deaf and Hard of Hearing 
People, 1988, El Paso, TX. 
15. Zazone P, Niemann LC, Gorenflo DW, et al. The health status and health care utilization of 
deaf and hard-of-hearing students. Arch Fam Med. 1993; 2:745-752.  
16. Kakalik JS, Furry WS, Thomas MA, Carney MF. The cost of special education.  Report to 
the U.S. Department of Education. Santa Monica, CA: RAND; 1981. US Dept. of Education 
publication no. N-1792-ED. 
17. Moore MT, Strang EW, Schwartz M, Braddock M. Patterns in special education service 
delivery and cost. Washington, DC: Decision Resources Corporation; 1988. 
18. Wolman J. Refunded CSEF to conduct new national study of special education expenditures. 
The CSEF resource. Palo Alto, CA: Center for Special Education Finance; 1999. 
19. Bess FH, Lichtenstein MJ, Logan SA, Burger MC, Nelson E. Hearing impairment as a 
determinant of function in the elderly. J Am Geriatr Soc. 1989; 37:123-128. 
20. Charatan FB. Depression in old age. NY State J Med. 1975; 75:2505-2509. 
21. Hodgson TA. Annual costs of illness versus lifetime costs of illness and implications for 
structural change. Drug Information Journal. 1988; 22:323-341. 

Nucleus 24 ABI in Non-NFII Children 
 
32
22. Bassim MK, Buss E, Clark MS, Kolln KA, Pillsbury CH, Pillsbury HC 3rd, Buchman CA. 
MED-EL Combi40+ cochlear implantation in adults. Laryngoscope. 2005 Sep; 115(9): 1568-
73. 
23. Niparko JK, Tobey EA, Thal DJ, Eisenberg LS, Wang NY, Quittner AL, Fink NE; CDaCI 
Investigative Team. Spoken language development in children following cochlear 
implantation. JAMA. 2010 Apr 21; 303(15): 1498-506. 
24. Barton GR, Stacey PC, Fortnum HM, Summerfield AQ. Hearing-impaired children in the 
United Kingdom, IV: cost-effectiveness of pediatric cochlear implantation. Ear Hear. 2006 
Oct; 27(5): 575-88.  
25. Francis HW, Chee N, Yeagle J, Cheng A, Niparko JK. Impact of cochlear implants on the 
functional health status of older adults. Laryngoscope. 2002 Aug; 112(8 Pt 1): 1482-8. 
26. Glastonbury CM, Davidson HC, Harnsberger HR, Butler J, Kertesz TR, Shelton C.  Imaging 
findings of cochlear nerve deficiency. AJNR Am J Neuroradiol. 2002 Apr; 23(4): 635-43. 
27. Adunka OF, Roush PA, Teagle HF, et al.  Internal auditory canal morphology in children with 
cochlear nerve deficiency. Otol Neurotol 2006; 27:793-801. 
28. Adunka OF, Jewells V, Buchman CA. Value of computed tomography in the evaluation of 
children with cochlear nerve deficiency. Otol Neurotol 2007; 28:597-604. 
29. Buchman CA, Roush PA, Teagle HF, Brown CJ, Zdanski CJ, Grose JH. Auditory neuropathy 
characteristics in children with cochlear nerve deficiency. Ear Hear 2006; 27:399-408. 
30. Buchman CA, Teagle HF, Roush PA, Park LR, Hatch D, Woodard J, Zdanski C, Adunka OF. 
Cochlear implantation in children with labyrinthine anomalies and cochlear nerve deficiency: 
implications for auditory brainstem implantation. Laryngoscope. 2011 Sep; 121(9): 1979-88.  
31. Valero J, Blaser S, Papsin BC, James AL, Gordon KA. Electrophysiologic and behavioral 
outcomes of cochlear implantation in children with auditory nerve hypoplasia. Ear Hear. 
2012 Jan-Feb; 33(1): 3-18. 
32. Kutz JW Jr, Lee KH, Isaacson B, Booth TN, Sweeney MH, Roland PS. Cochlear 
implantation in children with cochlear nerve absence or deficiency. Otol Neurotol. 2011 Aug; 
32(6): 956-61. 
33. Warren FM 3rd, Wiggins RH 3rd, Pitt C, Harnsberger HR, Shelton C. Apparent cochlear 
nerve aplasia: to implant or not to implant? Otol Neurotol. 2010 Sep; 31(7): 1088-94. 
34. Schwartz MS, Otto SR, Brackmann DE, Hitselberger WE, Shannon RV. Use of a multichannel 
auditory brainstem implant for neurofibromatosis type 2. Stereotact Funct Neurosurg 2003; 
81:110-114. 
35. Colletti V, Fiorino FG, Carner M, Giarbini N, Sacchetto L, Cumer G. The retrosigmoid 
approach for auditory brainstem implantation. Am J Otol 2000; 21:826-36.  
36. Colletti V, Fiorino F, Carner M, Sacchetto L, Miorelli V, Orsi A. Auditory brainstem 
implantation: the University of Verona experience. Otolaryngol Head Neck Surg 2002; 127:84-
96. 
37. Colletti V, Carner M, Miorelli V, Colletti L, Guida M, Fiorino F. Auditory brainstem implant in 
posttraumatic cochlear nerve avulsion. Audiol Neurotol 2004; 9:247-55. 
38. Colletti V, Carner M, Miorelli V, Guida M, Colletti L, Fiorino F. Auditory brainstem implant 
(ABI): new frontiers in adults and children. Otolaryngol Head Neck Surg 2005; 133:126-38. 
39. Colletti V. Auditory outcomes in tumor vs. nontumor patients fitted with auditory brainstem 
implants. Adv Otorhinolaryngol 2006; 64:167-185. 
40. Colletti V, Shannon R, Carner M, Veronese S, Colletti L. Outcomes in nontumor adults fitted 
with the auditory brainstem implant: 10 years' experience. Otol Neurotol 2009; 30:614-618. 

Nucleus 24 ABI in Non-NFII Children 
 
33
41. Colletti L, Zoccante L. Nonverbal cognitive abilities and auditory performance in children 
fitted with auditory brainstem implants: preliminary report. Laryngoscope. 2008 Aug; 
118(8): 1443-8. 
42. Sennaroglu L, Ziyal I, Atas A, Sennaroglu G, Yucel E, Sevinc S, Ekin MC, Sarac S, Atay G, 
Ozgen B, Ozcan OE, Belgin E, Colletti V, Turan E. Preliminary results of auditory brainstem 
implantation in prelingually deaf children with inner ear malformations including severe 
stenosis of the cochlear aperture and aplasia of the cochlear nerve. Otol Neurotol. 2009 Sep; 
30(6): 708-15. PubMed PMID: 19704357. 
43. Sennaroglu L, Ziyal I. Auditory brainstem implantation. Auris Nasus Larynx. 2011 Dec 21. 
[Epub ahead of print] PubMed PMID: 22196501. 
44. Toh EH, Luxford WM. Cochlear and brainstem implantation. 2002. Neurosurg Clin N Am. 
2008 Apr; 19(2): 317-29, vii. 
45. Laszig R, Marangos N, Sollmann WP, Ramsden RT. Central electrical stimulation of the 
auditory pathway in neurofibromatosis type 2. Ear Nose Throat J. 1999 Feb; 78(2): 110-1, 
115-7. 
46. Grayeli AB, Bouccara D, Kalamarides M, Ambert-Dahan E, Coudert C, Cyna-Gorse F, 
Sollmann WP, Rey A, Sterkers O. Auditory brainstem implant in bilateral and completely 
ossified cochleae. Otol Neurotol. 2003 Jan; 24(1): 79-82.  
47. Otto SR, Brackmann DE, Hitselberger WE, Shannon RV, Kuchta J. Multichannel auditory 
brainstem implant: update on performance in 61 patients. J Neurosurg. 2002 Jun; 96(6): 
1063-71. 
48. Colletti V, Shannon RV, Carner M, Veronese S, Colletti L. Complications in auditory 
brainstem implant surgery in adults and children. Otol Neurotol. 2010 Jun; 31(4): 558-64. 
49. Buchman CA, Adunka OF, Zdanski CJ, Pillsbury HC. Hearing loss in children: The 
otologist’s perspective. In: Comprehensive Handbook of Pediatric Audiology, Seewald and 
Tharpe (eds), Plural Publishing, 2011, San Diego, CA, Chapter 8: pp: 137-53. 
50. Wang NY, Eisenberg LS, Johnson KC, et al. Tracking development of speech recognition: 
longitudinal data from hierarchical assessments in the Childhood Development after 
Cochlear Implantation Study. Otol Neurotol 2008; 29: 240-245. 
51. Robbins AM, Renshaw JJ, Berry SW. Evaluating meaningful auditory integration in 
profoundly hearing-impaired children. Am J Otol. 1991; 12 Suppl: 144-50. 
52. Zimmerman-Phillips S, Robbins AM, Osberger MJ. Assessing cochlear implant benefit in 
very young children. Ann Otol Rhinol Laryngol Suppl. 2000 Dec; 185: 42-3. 
53. Moog, J.S. and Geers, A.E. (1990). Early Speech Perception Test for profoundly deaf 
hearing-impaired children.  St. Louis, Central Institute for the Deaf.  
54. Kirk KI, Pisoni DB, Osberger MJ. Lexical effects on spoken word recognition by pediatric 
cochlear implant users. Ear Hear. 1995 Oct; 16(5): 470-81. 
55. Haskins, H:  A phonetically balanced test of speech discrimination for children; unpublished 
master’s thesis, Evanston, 1949. 
56. Peterson GE, Lehiste I. Revised CNC lists for auditory tests. J Speech Hear Disord. 1962 
Feb; 27: 62-70. 
57. Fenson L, Dale P, Reznick JS, Thal D, Bates E, Harung J, Pethick S, Reilly J. The 
MacArthur Communicative Development Inventories: User’s guide and technical manual. 
San Diego, CA: Singular Publishing Group; 1993. 
58. Somri M, Coran AG, Hadjittofi C, Parisinos CA, Mogilner JG, Sukhotnik I, Gaitini L, Tome 
R, Matter I. Improved outcomes in paediatric anaesthesia: contributing factors. Pediatr Surg 
Int. 2012 Jun; 28(6): 553-61. 

Nucleus 24 ABI in Non-NFII Children 
 
34
59. Durham SR, Fjeld-Olenec K. Comparison of posterior fossa decompression with and without 
duraplasty for the surgical treatment of Chiari malformation Type I in pediatric patients: a 
meta-analysis. J Neurosurg Pediatr. 2008 Jul;2(1):42-9.