Department of Audiology and Speech Pathology, The University of Melbourne, Carlton, Victoria, Australia.
Murdoch Children's Research Institute, Parkville, Victoria, Australia.
JAMA Netw Open. 2021 Dec 1;4(12):e2136842. doi: 10.1001/jamanetworkopen.2021.36842.
Neurofibromatosis type 1 (NF1) affects hearing through disruption of central auditory processing. The mechanisms, functional severity, and management implications are unclear.
To investigate auditory neural dysfunction and its perceptual consequences in individuals with NF1.
DESIGN, SETTING, AND PARTICIPANTS: This case-control study included children and adults with NF1 and control participants matched on age, sex, and hearing level. Patients were recruited through specialist neurofibromatosis and neurogenetic outpatient clinics between April and September 2019. An evaluation of auditory neural activity, monaural/binaural processing, and functional hearing was conducted. Diffusion-weighted magnetic resonance imaging (MRI) data were collected from a subset of participants (10 children with NF1 and 10 matched control participants) and evaluated using a fixel-based analysis of apparent fiber density.
Type and severity of auditory dysfunction evaluated via laboratory testing and questionnaire data.
A total of 44 participants (18 [41%] female individuals) with NF1 with a mean (SD) age of 16.9 (10.7) years and 44 control participants (18 [41%] female individuals) with a mean (SD) age of 17.2 (10.2) years were included in the study. Overall, 11 participants (25%) with NF1 presented with evidence of auditory neural dysfunction, including absent, delayed, or low amplitude electrophysiological responses from the auditory nerve and/or brainstem, compared with 1 participant (2%) in the control group (odds ratio [OR], 13.03; 95% CI, 1.59-106.95). Furthermore, 14 participants (32%) with NF1 showed clinically abnormal speech perception in background noise compared with 1 participant (2%) in the control group (OR, 20.07; 95% CI, 2.50-160.89). Analysis of diffusion-weighted MRI data of participants with NF1 showed significantly lower apparent fiber density within the ascending auditory brainstem pathways. The regions identified corresponded to the neural dysfunction measured using electrophysiological assessment.
The findings of this case-control study could represent new neurobiological and clinical features of NF1. Auditory dysfunction severe enough to impede developmental progress in children and restrict communication in older participants is a common neurobiological feature of the disorder.
1 型神经纤维瘤病（NF1）通过中枢听觉处理的中断影响听力。其机制、功能严重程度和管理意义尚不清楚。
研究 NF1 个体的听觉神经功能障碍及其感知后果。
设计、设置和参与者：本病例对照研究纳入了 NF1 患儿和成人以及年龄、性别和听力水平匹配的对照组参与者。患者于 2019 年 4 月至 9 月通过神经纤维瘤病和神经遗传门诊招募。对听觉神经活动、单耳/双耳处理和功能听力进行评估。从一部分参与者（10 名 NF1 儿童和 10 名匹配的对照组参与者）中收集弥散加权磁共振成像（MRI）数据，并使用纤维密度固定分析进行评估。
通过实验室测试和问卷调查数据评估听觉功能障碍的类型和严重程度。
共纳入 44 名参与者（18 名[41%]女性），其中 NF1 患者平均（SD）年龄为 16.9（10.7）岁，44 名对照组参与者（18 名[41%]女性）平均（SD）年龄为 17.2（10.2）岁。总体而言，与对照组的 1 名参与者（2%）相比，11 名（25%）NF1 患者出现听觉神经功能障碍的证据，包括听觉神经和/或脑干的电生理反应缺失、延迟或幅度降低，而对照组的 1 名参与者（2%）（比值比[OR]，13.03；95%CI，1.59-106.95）。此外，与对照组的 1 名参与者（2%）相比，14 名（32%）NF1 患者在背景噪声中出现临床异常言语感知（OR，20.07；95%CI，2.50-160.89）。对 NF1 参与者的弥散加权 MRI 数据分析显示，上升性听觉脑干通路内的表观纤维密度明显降低。确定的区域与使用电生理评估测量的神经功能障碍相对应。
本病例对照研究的结果可能代表 NF1 的新神经生物学和临床特征。在儿童中严重到足以阻碍发育进展，在大龄参与者中严重到足以限制交流的听觉功能障碍是该疾病的常见神经生物学特征。
