Rationale: The overall goal of this 2022 NFRP research proposal is to enhance hearing in deaf patients from neurofibromatosis type 2 (NF2). The growth of bilateral vestibular schwannomas results in progressive and permanent hearing loss in almost all NF2 patients. The only option for providing hearing to deaf NF2 individuals when hearing aids or cochlear implants (CIs) are not helpful is the auditory brainstem implant (ABI). The FDA-approved the ABI in the U.S. almost two decades ago for patients with NF2. The ABI is inserted (usually during tumor surgery) through a craniotomy approach to provide hearing sensations. The surgeon must place the ABI blindly using surrounding brain landmarks and rely on live electrical recording feedback as the target of the ABI, called the “cochlear nucleus,” is not directly seen. Most NF2 ABI patients have sound awareness that improves lip-reading accuracy, but only rarely do they understand speech without any visual cues. In addition, NF2 ABI users often experience side effects, requiring the audiologist to turn off one or several channels on the device. This modest performance seen with the ABI can be explained by (a) tumor growth that damages the brainstem, (b) challenging nature of the surgery in which there are no direct ways to “see” that the ABI is in the correct location, (c) limitations in our ability to program ABIs, and (d) the rigid design of the clinical ABI that does not allow it to wrap around curved brain tissue.

Objectives/Aims: To solve these unmet needs, our work seeks to enhance NF2 ABI outcomes by:

Aim 1. Predicting the best auditory performance based on detailed ABI location seen on three-dimensional (3D) CT (a technique that our group developed), as well as on 3D MRI scans and routine X-ray views. We will apply this new and exciting composite imaging technique on NF2 patients from Massachusetts Eye and Ear as well as from several more clinics in the U.S. and abroad to improve our ability to see different trends in the data with a greater number of patients. In addition, we will be applying artificial intelligence techniques to these data to more effectively test our predictive model of NF2 ABI user performance.

Aim 2. Developing new ways to test NF2 ABI patients and improve programming techniques to enhance hearing. We will use existing and new approaches to assess hearing with the ABI and determine how these responses agree with the ideal positioning of the device as described in Aim 1.

Aim 3. Using a mouse model of NF2 to better understand how a new-generation soft ABI stimulates the cochlear nucleus and provides hearing compared to a mouse model that lacks brain tumors. There are a number of important questions about the ABI that we will answer in Aim 3, including (1) what nerves are activated with the ABI and where are they located and (2) what is the effect of tumor growth on ABI responses in a mouse with NF2 compared to a normal mouse that does not have brain tumors? Advancing our knowledge about how the ABI works will help inform how we program the device as defined in Aim 2, and will also influence future designs of flexible ABI technology for use in human.

Target population: NF2 patients who are candidates or users of the ABI

Clinical Application/Timeline: A major strength of our proposal is the immediate potential for clinical translation. The “ideal” position of the ABI defined in Aim 1 can readily be used during surgery to guide placement, especially given the availability of surgical CT navigation technology and portable X-rays in the operating room, including at our institution. Optimizing the testing and programming of the ABI seen in Aim 2 can also be translated to our existing NF2 ABI user population. In addition, though more long-term in perspective, the flexible electrode and novel biomaterials used in Aim 3 have already been extensively tested in animal models by our research team, and we will exploit the benefits of this soft design to answer basic questions about how the ABI provides hearing in NF2.

Overall Impact/Contribution: It is extremely disappointing to offer an NF2 patient who is deaf a hearing implant that provides modest benefits and little to no speech recognition, unlike the CI or a hearing aid. Despite these limitations, the ABI device and its surgical implantation and programming techniques have remained largely unchanged since its initial development 30 years ago. Our proposal brings together a multi-disciplinary, multi-institutional team to address this neglected area of NF2 research and improve hearing abilities and quality of life for deaf NF2 patients.