Madhani Amsal S, King Susan, Zhu Jennifer, Karmali Faisal, Welling D Bradley, Cai Wenli, Jordan Justin T, Lewis Richard F
Department of Otolargynology, Massachusetts Eye and Ear, Boston, MA, USA.
Department of Otolaryngology Head and Neck Surgery, Harvard Medical School, Boston, MA, USA.
Brain Commun. 2023 Mar 23;5(2):fcad089. doi: 10.1093/braincomms/fcad089. eCollection 2023.
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.
2型神经纤维瘤病相关的神经鞘瘤病是一种遗传性疾病，其特征为神经系统肿瘤，最常见的是起源于前庭蜗神经的前庭神经鞘瘤。尽管前庭症状可能会使人丧失能力，但2型神经纤维瘤病相关的神经鞘瘤病从未对前庭功能进行过仔细分析。此外，化疗（如贝伐单抗）可减小2型神经纤维瘤病相关的神经鞘瘤病患者的肿瘤体积并改善听力，但对其前庭效应却一无所知。在本报告中，我们研究了8例未经治疗的2型神经纤维瘤病相关的神经鞘瘤病患者的三种主要前庭介导行为（眼球运动、运动感知和平衡）、临床前庭功能障碍（头晕和共济失调）以及影像学和听力情况，并将其结果与正常受试者以及散发的单侧前庭神经鞘瘤患者进行了比较。我们还研究了贝伐单抗对2例2型神经纤维瘤病相关的神经鞘瘤病患者的影响。2型神经纤维瘤病相关的神经鞘瘤病中的前庭神经鞘瘤降低了前庭精度（变异性的倒数，反映中枢信噪比降低），但未影响前庭准确性（相对于理想幅度的幅度，反映中枢信号幅度），并导致临床功能障碍。贝伐单抗改善了2例2型神经纤维瘤病相关的神经鞘瘤病患者的前庭精度和临床功能障碍，但未影响前庭准确性。这些结果表明，我们研究的2型神经纤维瘤病相关的神经鞘瘤病患者群体中的前庭神经鞘瘤降低了中枢前庭信噪比，而贝伐单抗提高了信噪比，这些变化可以通过传入神经噪声的增加（神经鞘瘤）和抑制（贝伐单抗）从机制上进行解释。
