Mitochondrial encephalomyopathy involves ophthalmology otorhinolaryngology neurology and their clinical features
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摘要: 目的 探讨线粒体脑肌病(MEM)的耳鼻咽喉科临床特点, 结合眼科及神经内科临床表现, 为该病的早期诊治提供依据。方法 2001年9月-2020年1月确诊为MEM的28例患者。采集所有受试者的眼耳鼻咽喉科及神经内科相关的家族史、临床症状。检查: 纯音听阈, 声导抗, 畸变产物耳声发射, 听性脑干反应, 耳蜗微电位, 言语识别率; 面肌电图, 喉肌电图, 四肢肌电图及心电图; 颞骨CT, 颅脑MRI平扫加增强; 肌肉活检; mtDNA基因检测。结果 所有患者经肌肉活检和(或)mtDNA基因检测证实为MEM。半数有母系遗传史。耳鼻咽喉科症状: 听力损失15例(53.6%), 耳鸣4例(14.3%), 听觉失认1例(3.6%), 面肌无力4例(14.3%), 吞咽困难3例(10.7%)。眼科及神经内科症状: 上睑下垂16例(57.1%), 视神经萎缩15例(53.6%), 运动不耐受16例(57.1%), 肌肉萎缩6例(21.4%), 卒中样发作5例(17.9%)。听力损失为感音神经性, 表现为听阈提高15例(53.6%), 声导抗均正常, 畸变产物耳声发射未引出18例(64.3%), 听性脑干反应阈值提高18例(64.3%), 耳蜗微电位均未记录到, 言语识别率下降6例(21.4%)。面肌电图异常4例(14.3%), 喉肌电图异常3例(10.7%), 四肢肌电图异常6例(21.4%), 心电异常8例(28.6%)。颞骨CT均正常, 颅脑MRI显示异常改变19例(67.9%), 包括中枢神经脱髓鞘8例(28.6%)、脑白质发育不良6例(21.4%)、脑萎缩5例(17.9%)、多发腔隙性脑梗死改变4例(14.3%)、基底节钙化1例(3.6%)。结论 MEM常见上睑下垂、视听功能障碍、运动不耐受、肌肉萎缩及卒中样发作等眼耳鼻咽喉科及神经内科的多系统损害。耳鼻咽喉科特点为青少年期起病的感音神经性听力损失, 多数为双侧对称性渐进性, 少数为突聋、急性耳鸣、听觉失认。临床许多不明原因、伴有多系统损害的听力损失患者应考虑做mtDNA基因检测。中年以后逐渐加重的面肌无力和吞咽困难者应做肌肉活检。耳声发射和听性脑干反应比主观检查更敏感, 听力监测有助于评估病程进展。Abstract: Objective This study aimed to provide better understanding of the otolaryngologic features, combined with ophthalmologic and neurologic characteristics in mitochondrial encephalomyopathy(MEM), and to help ENT and auditory practitioner making correct diagnosis as well.Methods Twenty-eight patients with MEM were enrolled between September 2001 and January 2020. Information about family histories and clinical symptoms was retrospectively analyzed. All patients underwent otorhinolaryngological, ophthalmological and neurological examinations, including: pure-tone audiometry, acoustic immittance(AI), distortion-product otoacoustic emissions(DPOAE), auditory brainstem response(ABR), cochlear micropotential(CM), speech discrimination score(SDS), electroneurography(ENoG), computed tomography(CT) of the temporal bone and cranial magnetic resonance weighted imaging scan(MRI), muscle biopsy and mtDNA gene testing.Results ENT subjective manifestations were present in 15 cases (53.6%) with sensorineural hearing loss(SNHL), 4(14.3%) with tinnitus, 4(14.3%) with facial weakness, 3(10.7%) with dysphagia, 1(3.6%) with auditory agnosia. Ophthalmological and neurological symptoms included ptosis in 16 cases (57.1%), exercise intolerance in 16(57.1%), optic atrophy in 15(53.6%), muscular atrophy in 6(21.4%), and stroke-like episodes in 5(17.9%). The results of objective examinations were as follows: DPOAE were not elicited in 18(64.3%) cases, ABR abnormalities in 18(64.3%) cases, hearing threshold shift in 15(53.6%) cases, AI normal and CM was not detected in all cases, SDS decreased in 6(21.4%) cases, facial ENoG abnormalities in 4(14.3%) cases, laryngeal ENoG abnormalities in 3(10.7%) cases, EMG abnormalities in 6(21.4%) cases, and ECG abnormalities in 8(28.6%) cases. Temporal CT were normal, but cranial MRI abnormalities were found in 19 cases(67.9%), including central nerve demyelination, white matter hyperintensities, generalized cerebellar and cerebral atrophy, multiple cortical/subcortical infarct-like lesions, basal ganglia calcification.Conclusion Multisystemic syndromes in MEM can present as a variety of otolaryngological, ophthalmological and neurological abnormalities, such as ptosis, audio-visual disturbance, exercise intolerance and stroke-like episodes etc. SNHL, tinnitus, auditory agnosia, facial weakness and dysphagia were ENT specific manifestations. SNHL in MEM is bilateral symmetrical progressive or of sudden onset since teenage. mtDNA testing may be helpful for adolescent patient whose SNHL was associated with neuromuscular symptoms. Muscle biopsy should be considered when middle-aged patients developed facial weakness and dysphagia. DPOAE and ABR are the optimal objective audiometric tests to monitor the progression of MEM associated with SNHL.
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Key words:
- mitochondrial encephalomyopathy /
- hearing loss /
- tinnitus /
- facial weakness /
- dysphagia
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表 1 MEM临床表现
例(%) 首发表现 频率 伴发表现 神经肌肉系统 频率 非神经肌肉系统 频率 上睑下垂 16(57.1) 眼外肌麻痹 11(39.3) 急性期发热 4(14.3) 运动不耐受 9(32.1) 听力下降 9(32.1) 身材矮小 4(14.3) 视力下降 8(28.6) 运动不耐受 7(25.0) 低体重指数 4(14.3) 听力下降 6(21.4) 心慌 7(25.0) 呕吐 3(10.7) 卒中样发作 5(17.9) 面肌无力 4(14.3) 腹泻或便秘 2(7.1) 耳鸣 4(14.3) 智力障碍 4(14.3) 糖尿病 2(7.1) 智力障碍 4(14.3) 精神行为异常 4(14.3) 抑郁症 2(7.1) 白内障 3(10.7) 偏盲 3(10.7) 肾脏损害 1(3.6) 复视 3(10.7) 青光眼 3(10.7) 性腺功能低下 1(3.6) 眼痛 3(10.7) 头晕 3(10.7) 头痛 3(10.7) 肢体麻木 2(7.1) 吞咽困难 2(7.1) 失语 2(7.1) 糖尿病 2(7.1) 吞咽困难 1(3.6) 听觉失认 1(3.6) 视幻觉 1(3.6) 失眠 1(3.6) 
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表 2 MEM各亚型PTA
例 诊断 听力正常 听力损失 合计 轻度 中度 重度 极重度 CPEO 10 1 1 2 1 15 MELAS 1 0 1 2 1 5 KSS 1 1 1 2 0 5 MIDD 0 1 1 0 0 2 LHON 1 0 0 0 0 1 合计 13 3 4 6 2 28
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表 3 MEM各亚型听力检查
例 诊断 PTA正常 PTA异常 声导抗 DPOAE正常 ABR正常 SDS正常 声导抗 DPOAE异常 ABR异常 SDS异常 鼓室图正常 ASR正常 鼓室图正常 ASR异常 CPEO 10 10 7 8 10 5 4 5 5 5 MELAS 1 1 1 1 0 4 4 4 4 4 KSS 1 1 1 0 1 4 3 4 4 4 MIDD 0 0 0 0 0 2 1 2 2 2 LION 1 1 1 1 1 0 0 0 0 0
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