Peripheral Nerve Dysfunction in Middle-Aged Subjects Born with Thalidomide Embryopathy

BackgroundPhocomelia is an extremely rare congenital malformation that emerged as one extreme of a range of defects resulting from in utero exposure to thalidomide. Individuals with thalidomide embryopathy (TE) have reported developing symptoms suggestive of peripheral nervous system dysfunction in the mal-developed limbs in later life.MethodsCase control study comparing TE subjects with upper limb anomalies and neuropathic symptoms with healthy controls using standard neurophysiological testing. Other causes of a peripheral neuropathy were excluded prior to assessment.ResultsClinical examination of 17 subjects with TE (aged 50.4±1.3 [mean±standard deviation] years, 10 females) and 17 controls (37.9±9.0 years; 8 females) demonstrated features of upper limb compressive neuropathy in three-quarters of subjects. Additionally there were examination findings suggestive of mild sensory neuropathy in the lower limbs (n = 1), L5 radiculopathic sensory impairment (n = 1) and cervical myelopathy (n = 1). In TE there were electrophysiological changes consistent with a median large fibre neuropathic abnormality (mean compound muscle action potential difference -6.3 mV ([-9.3, -3.3], p = 0.0002) ([95% CI], p-value)) and reduced sympathetic skin response amplitudes (-0.8 mV ([-1.5, -0.2], p = 0.0089)) in the affected upper limbs. In the lower limbs there was evidence of sural nerve dysfunction (sensory nerve action potential -5.8 μV ([-10.7, -0.8], p = 0.0232)) and impaired warm perception thresholds (+3.0°C ([0.6, 5.4], p = 0.0169)).ConclusionsWe found a range of clinical features relevant to individuals with TE beyond upper limb compressive neuropathies supporting the need for a detailed neurological examination to exclude other treatable pathologies. The electrophysiological evidence of large and small fibre axonal nerve dysfunction in symptomatic and asymptomatic limbs may be a result of the original insult and merits further investigation.

背景
海豹肢畸形（Phocomelia）是一种极为罕见的先天性畸形，是宫内暴露于沙利度胺（thalidomide）所引发的一系列出生缺陷的极端表型之一。沙利度胺胚胎病（thalidomide embryopathy, TE）患者在后续生命中，曾被报道出现发育畸形肢体伴周围神经系统功能障碍的相关症状。

方法
本研究为病例对照研究，纳入伴上肢畸形与神经病变症状的TE患者作为病例组，以健康个体作为对照组，采用标准化神经生理学检测进行对比分析。所有受试者在评估前均已排除其他可引发周围神经病的病因。

结果
对17例TE患者（年龄50.4±1.3岁[均值±标准差]，女性10例）及17例健康对照者（年龄37.9±9.0岁，女性8例）进行临床检查，结果显示四分之三的患者存在上肢压迫性神经病的特征。此外，检查结果还提示1例患者存在下肢轻度感觉性神经病、1例存在L5神经根病性感觉障碍，另有1例存在颈髓病。在受累上肢中，TE患者的电生理改变符合正中神经大纤维神经病性异常表现：复合肌肉动作电位均值差为-6.3 mV（95%置信区间[-9.3, -3.3]，p=0.0002），交感皮肤反应波幅降低（均值差-0.8 mV，95%置信区间[-1.5, -0.2]，p=0.0089）。在下肢中，检测发现腓肠神经功能异常：感觉神经动作电位均值差为-5.8 μV（95%置信区间[-10.7, -0.8]，p=0.0232），温热感知阈值受损（均值差+3.0℃，95%置信区间[0.6, 5.4]，p=0.0169）。

结论
本研究发现，TE患者除上肢压迫性神经病外，还存在一系列其他相关临床特征，这提示需对患者进行全面的神经系统检查，以排除其他可治疗的病理情况。在有症状及无症状肢体中均检测到大、小纤维轴索神经功能障碍的电生理证据，这可能源于初始的胚胎损伤，值得进一步深入研究。