Vestibular dysfunction in neurofibromatosis type 2-related schwannomatosis

Amsal S Madhani; Susan King; Jennifer Zhu; Faisal Karmali; D Bradley Welling; Wenli Cai; Justin T Jordan; Richard F Lewis

doi:10.1093/braincomms/fcad089

Vestibular dysfunction in neurofibromatosis type 2-related schwannomatosis

Brain Commun. 2023 Mar 23;5(2):fcad089. doi: 10.1093/braincomms/fcad089. eCollection 2023.

Authors

Amsal S Madhani¹, Susan King¹, Jennifer Zhu¹, Faisal Karmali^{1

2}, D Bradley Welling^{1

2}, Wenli Cai^{3

4}, Justin T Jordan^{3

5}, Richard F Lewis^{1

2

3

5}

Affiliations

¹ Department of Otolargynology, Massachusetts Eye and Ear, Boston, MA, USA.
² Department of Otolaryngology Head and Neck Surgery, Harvard Medical School, Boston, MA, USA.
³ Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
⁴ Department of Radiology, Harvard Medical School, Boston, MA, USA.
⁵ Department of Neurology, Harvard Medical School, Boston, MA, USA.

Abstract

Neurofibromatosis type 2-related schwannomatosis is a genetic disorder characterized by neurologic tumours, most typically vestibular schwannomas that originate on the vestibulo-cochlear nerve(s). Although vestibular symptoms can be disabling, vestibular function has never been carefully analysed in neurofibromatosis type 2-related schwannomatosis. Furthermore, chemotherapy (e.g. bevacizumab) can reduce tumour volume and improve hearing in neurofibromatosis type 2-related schwannomatosis, but nothing is known about its vestibular effects. In this report, we studied the three primary vestibular-mediated behaviours (eye movements, motion perception and balance), clinical vestibular disability (dizziness and ataxia), and imaging and hearing in eight untreated patients with neurofibromatosis type 2-related schwannomatosis and compared their results with normal subjects and patients with sporadic, unilateral vestibular schwannoma tumours. We also examined how bevacizumab affected two patients with neurofibromatosis type 2-related schwannomatosis. Vestibular schwannomas in neurofibromatosis type 2-related schwannomatosis degraded vestibular precision (inverse of variability, reflecting a reduced central signal-to-noise ratio) but not vestibular accuracy (amplitude relative to ideal amplitude, reflecting the central signal magnitude) and caused clinical disability. Bevacizumab improved vestibular precision and clinical disability in both patients with neurofibromatosis type 2-related schwannomatosis but did not affect vestibular accuracy. These results demonstrate that vestibular schwannoma tumours in our neurofibromatosis type 2-related schwannomatosis population degrade the central vestibular signal-to-noise ratio, while bevacizumab improves the signal-to-noise ratio, changes that can be explained mechanistically by the addition (schwannoma) and suppression (bevacizumab) of afferent neural noise.

Keywords: balance; dizziness; neurofibromatosis; schwannoma; vestibular.

Grants and funding

R01 DC018287/DC/NIDCD NIH HHS/United States