Mechanisms of Hearing Loss in Neurofibromatosis Type 2

Abstract

IntroductionPatients with neurofibromatosis type 2 (NF2) develop bilateral cochleovestibular schwannomas (CVSs) that cause binaural deafness in most individuals. Hearing loss occurs in an unpredictable manner and the underlying mechanisms are not known. To gain insight into the pathophysiologic basis for hearing loss in NF2, we performed a prospective cross-sectional study of untreated ears in NF2 patients.MethodsOne hundred consecutive NF2 patients in a prospective natural history study were included. Clinical and audiometric data were analyzed for treatment naïve ears. In addition to standard MR-imaging sequences, alterations in intralabyrinthine protein content were determined utilizing high resolution FLAIR, the presence of cochlear aperture obstruction was determined by examining 3D T2 sequences, and endolymphatic hydrops was identified on delayed post-contrast FLAIR sequences.ResultsEighty-nine ears harboring 84 untreated CVSs in 56 consecutive NF2 patients (age 30±16 years) were analyzed. Thirty-four (38%) ears had varying degrees of hearing loss. Elevated intralabyrinthine protein was identified in 70 (75%) ears by FLAIR MR-imaging and was strongly associated with the presence of hearing loss (32/34 hearing loss ears; 94%)(Fisher's exact test; P = .005). Elevated intralabyrinthine protein was associated with the presence of CVS-associated cochlear aperture obstruction (64 of 67 ears with elevated protein; 96%)(Fisher's exact test; P<0.0001) in both normal and hearing loss ears. Elevated intralabyrinthine protein was not identified in ears without CVS (5 ears). While larger tumor size was associated with hearing loss (P = 0.006), 16 hearing loss ears (47%) harbored CVSs less than 0.5 cm3, including 14 ears (88%) with block of the cochlear aperture and elevated protein.DiscussionThese findings are consistent with a model in which hearing loss develops as a result of cochlear aperture obstruction and accumulation of intralabyrinthine protein. MRI based identification of elevated intralabyrinthine protein may help identify the ear at-risk for developing hearing loss.

Natural History of Vestibular Schwannoma Growth and Hearing Decline in Newly Diagnosed Neurofibromatosis Type 2 Patients

“…For this reason, we propose that NF2 patients with VS ≥ 1 ml be stratified as "high risk" for subsequent hearing decline, and that consideration be given to making these patients eligible for trials without the need for documented tumor progression at study enrollment. Emerging techniques such as radiographic identification of elevated intralabrynthine protein 28 may suggest new strategies to further supplement selection of patients at highest risk for hearing loss.…”

Audiovestibular Characteristics of Small Cochleovestibular Schwannomas in Neurofibromatosis Type 2

“…15 T2-3D TSE with Variable Flip Angle (VISTA) magnetic resonance images were performed to detect cochlear aperture obstruction, as defined by the absence of a patent cerebrospinal fluid (CSF) pathway between the posterior fossa and the cochlear aperture (cochlear nerve entry point into the modiolus) ( Figure 1C). 10 Volume of the tumors was determined using postcontrast T1-weighted images and the following formula: volume = (maximum anteroposterior dimension 3 maximum mediallateral dimension 3 maximum craniocaudal dimension)/ 2. 16,17 Canalicular and posterior fossa components, if present, were summed for total CVS volume.…”

Progress of hearing loss in neurofibromatosis type 2: implications for future management

“…These suggest that hearing deteriorates by approximately 3 dB/year. Studies investigating NF2 patients are fewer in number but suggest the rate of hearing loss is similar with an annual change in pure tone average of around 4 dB and an annual change in speech discrimination scores of around 2 % [6,9,[22][23][24]. Only a recent study by Peyre et al [23] present preservation of hearing serviceability data and they state a figure of 74 % over a 72-month period on average.…”

“…In addition, it is likely that there are fewer undiagnosed vestibular schwannomas in NF2 than with sporadic tumours because of greater vigilance and screening. The clinical incidence of sporadic vestibular schwannomas is 1/10,000 whereas pathological studies have found the incidence of vestibular schwannomas to be significantly higher (0.57-2.7 %) [22,25,26]. It is, therefore, likely that a significant proportion of sporadic vestibular schwannomas remain asymptomatic or undiagnosed.…”