Posted December 6, 2023

Daniel J. Lee, Ph.D., Massachusetts Eye and Ear

Neurofibromatosis type 2 (NF2) is a genetic disorder in which benign, slow-growing tumors develop throughout the central nervous system. According to the Neurofibromatosis Clinics Association, NF2 affects an estimated one in 25,000 people. An estimated 90%-95% of NF2 patients develop bilateral tumors on the balance nerves connected to the inner ear, called vestibular schwannomas, according to the National Institute on Deafness and Other Communication Disorders. In most patients, these tumors are associated with profound hearing loss in one or both ears. The auditory brainstem implant (ABI) is the only approved hearing loss therapy for NF2 patients in the United States, but its effectiveness is limited for most users. Currently, surgeons are unable to see the target of the ABI directly during surgery and rely entirely on indirect physical “landmarks” around the brainstem and electrical responses to ensure accurate placement. Furthermore, the stiff “paddle” design of the ABI’s electrode array – based on a design that is more than 20 years old – often results in inconsistent contact with the brainstem. As a result, ABI users only rarely experience meaningful gains in speech understanding and often experience unpleasant physical side effects.

Improvements in ABI surgical methods and device design could lead to significantly better hearing outcomes for deaf NF2 patients. With the help of a fiscal year 2017 (FY17) Neurofibromatosis Research Program Investigator-Initiated Research Award – Optional Qualified Collaborator, Dr. Daniel Lee explored whether three-dimensional (3D) computed tomography (CT) imaging could be used to identify the optimal placement of the ABI’s electrode array on the cochlear nucleus, the part of the brainstem that first receives the signals transmitted by the auditory nerve. Dr. Lee’s team also sought to develop a new flexible electrode array that would allow ABIs to conform to the shape of the brainstem, resulting in improved performance.

Dr. Lee’s team used 3D CT imaging to correlate the placement of the ABI sensory array with hearing and speech comprehension in two groups of ABI users, most of whom had been diagnosed with NF2. They also tested pitch perception in a group of 16 ABI users. The results of these experiments enabled the researchers to make significant progress toward identifying the optimal position, orientation, shape, and electrical current threshold of the new “soft” ABI for achieving the best hearing outcomes in NF2 patients. These data were used to create a 3D model of the ABI electrode array that surgeons can use in conjunction with individual patient data to ensure the optimal implant placement and orientation of the ABI on the cochlear nucleus.

The team used 3D CT scan data, X-rays, and magnetic resonance imaging (MRI) to design and fabricate soft ABIs that conform to the curvature of the cochlear nucleus. Because soft ABIs are harder to manipulate due to their small size and flexibility, the team also designed and tested temporary insertion guides to help surgeons place them accurately. The insertion guides are bioresorbable – that is, they are made of biologically safe polymers that slowly dissolve in cerebral spinal fluid after approximately two hours. The researchers conducted test implants of soft ABIs using insertion guides in patients and cadaveric specimens to validate the placement on cochlear nuclei. As a result of these successful research outcomes, in FY22, Dr. Lee received an Investigator-Initiated Research Award – Funding Level 3 – Optional Qualified Collaborator – NF Open Science Initiative to assemble a multidisciplinary team across several institutions to further develop the new, improved ABI for clinical applications. This new research program will collect 3D CT, X-ray, and MRI data on NF2 patients from multiple institutions to further refine trends they have identified previously with a higher degree of fidelity, as well as apply artificial intelligence to these data to test their predictive model of ABI performance in NF2 patients. They will also develop improved testing and programming techniques that will help them further refine ABI placement on the cochlear nucleus, and use mouse models of NF2 to help them better understand how ABI placement and tumor growth affect speech recognition ability and quality.

Because it relies on existing surgical techniques and proven materials, Dr. Lee’s research promises immediate translation into clinical use. By addressing this long-neglected area of NF2 research, Dr. Lee’s research could lead to significant improvements in the quality of life for deaf NF2 patients.

References:
Neurofibromatosis Clinics Association. Facts & Statistics.
https://nfpittsburgh.org/whatisnf/facts-statistics/

National Institute on Deafness and Other Communication Disorders. Vestibular Schwannoma (Acoustic Neuroma) and Neurofibromatosis.
https://www.nidcd.nih.gov/health/vestibular-schwannoma-acoustic-neuroma-and-neurofibromatosis

Publication:
Egra-Dagan D, van Beurden I, Barber SR et al. 2021. Adult auditory brainstem implant outcomes and three-dimensional electrode array position on computed tomography. Ear Hear 42(6):1741-1754. https://doi.org/10.1097/AUD.0000000000001064

Links:
Public and Technical Abstracts: Improving Hearing in NF2 Patient Who Use the Auditory Brainstem Implant (ABI)

Public and Technical Abstracts: Multicenter Study for Enhancing Auditory Brainstem Implant (ABI) Performance in Neurofibromatosis type 2 (NF2) Patients

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