Data_Sheet_1_Co-occurrence of Hyperacusis Accelerates With Tinnitus Burden Over Time and Requires Medical Care.docx

Although tinnitus represents a major global burden, no causal therapy has yet been established. Ongoing controversies about the neuronal pathophysiology of tinnitus hamper efforts in developing advanced therapies. Hypothesizing that the unnoticed co-occurrence of hyperacusis and differences in the duration of tinnitus may possibly differentially influence the neural correlate of tinnitus, we analyzed 33 tinnitus patients without (T-group) and 20 tinnitus patients with hyperacusis (TH-group). We found crucial differences between the T-group and the TH-group in the increase of annoyance, complaints, tinnitus loudness, and central neural gain as a function of tinnitus duration. Hearing thresholds did not differ between T-group and TH-group. In the TH-group, the tinnitus complaints (total tinnitus score) were significantly greater from early on and the tinnitus intensity distinctly increased over time from ca. 12 to 17 dB when tinnitus persisted more than 5 years, while annoyance responses to normal sound remained nearly constant. In contrast, in the T-group tinnitus complaints remained constant, although the tinnitus intensity declined over time from ca. 27 down to 15 dB beyond 5 years of tinnitus persistence. This was explained through a gradually increased annoyance to normal sound over time, shown by a hyperacusis questionnaire. Parallel a shift from a mainly unilateral (only 17% bilateral) to a completely bilateral (100%) tinnitus percept occurred in the T-group, while bilateral tinnitus dominated in the TH-group from the start (75%). Over time in the T-group, ABR wave V amplitudes (and V/I ratios) remained reduced and delayed. By contrast, in the TH-group especially the ABR wave III and V (and III/I ratio) continued to be enhanced and shortened in response to high-level sound stimuli. Interestingly, in line with signs of an increased co-occurrence of hyperacusis in the T-group over time, ABR wave III also slightly increased in the T-group. The findings disclose an undiagnosed co-occurrence of hyperacusis in tinnitus patients as a main cause of distress and the cause of complaints about tinnitus over time. To achieve urgently needed and personalized therapies, possibly using the objective tools offered here, a systematic sub-classification of tinnitus and the co-occurrence of hyperacusis is recommended.

尽管耳鸣已成为全球性重大健康负担，但目前尚未确立任何针对病因的治疗方案。关于耳鸣神经元病理生理学的持续争议，阻碍了先进治疗方案的研发进程。本研究假设，未被察觉的听觉过敏（hyperacusis）共病情况以及耳鸣病程时长的差异，可能会对耳鸣的神经关联物产生不同影响。据此，我们分析了33名不伴听觉过敏的耳鸣患者（T组）与20名伴听觉过敏的耳鸣患者（TH组）。
研究发现，随着耳鸣病程的延长，T组与TH组在烦恼程度、主诉症状、耳鸣响度以及中枢神经增益的变化上存在显著差异。两组患者的听阈值并无显著差异。
在TH组中，耳鸣相关主诉（耳鸣总评分）从病程早期便显著更高；且当耳鸣病程超过5年时，耳鸣强度随时间推移从约12 dB显著升高至17 dB，而对正常声音的烦恼反应几乎保持不变。与之相反，T组的耳鸣相关主诉始终保持稳定，尽管当耳鸣病程超过5年时，耳鸣强度随时间从约27 dB下降至15 dB。这一现象可通过听觉过敏问卷所反映的、随时间推移对正常声音的烦恼程度逐渐升高得到解释。
同时，T组的耳鸣感知从以单侧为主（仅17%为双侧）完全转变为双侧耳鸣（100%）；而TH组从病程早期便以双侧耳鸣为主（75%）。随着病程推移，T组的听性脑干反应（ABR）V波振幅（及V/I波幅比）始终处于降低且潜伏期延迟的状态。与之相反，TH组尤其是其ABR的III、V波（及III/I波幅比）在接受高强度声音刺激时，振幅持续升高且潜伏期缩短。值得注意的是，与T组随病程推移听觉过敏共病率升高的迹象相符，其ABR III波振幅也出现了小幅升高。
本研究结果表明，耳鸣患者中未被诊断出的听觉过敏共病情况，是导致患者痛苦以及随时间推移出现耳鸣相关主诉的主要原因。为了实现亟需的个性化治疗（可借助本研究提供的客观检测工具），建议对耳鸣及其伴发的听觉过敏进行系统性亚分类。