面部瘙痒和僵硬作为甘氨酸受体抗体阳性伴僵直和肌阵挛的进行性脑脊髓炎的初始表现：一例病例报告及文献复习

文献信息

中文摘要

背景： 伴僵直和肌阵挛的进行性脑脊髓炎（PERM）是僵人谱系障碍（SPSD）中一种罕见且严重的表型，常与甘氨酸受体抗体（GlyR-Ab）相关。由于疾病起病时可能缺乏典型的僵硬和刺激敏感性痉挛，早期诊断可能具有挑战性。方法：我们报告一名52岁男性，表现为面部瘙痒、面部僵硬、舌伸出受限、吞咽困难和左下肢疼痛。早期表现包括复视、眼球运动受限、构音障碍、张口受限、类似牙关紧闭的不自主下颌闭合以及不自主咬舌。影像学上的非特异性口咽和颌面部异常最初引起对感染性多发性颅神经病、破伤风或口面部感染的担忧；然而，抗菌治疗以及地西泮和普瑞巴林的 symptomatic 治疗未产生持续改善。随后出现颈部、躯干和下肢僵硬、步态障碍、口周感觉过敏和刺激诱发的面部肌肉收缩，促使重新考虑SPSD。结果：针极肌电图（EMG）显示静息状态下主动肌和拮抗肌存在持续同步的运动单位活动。血清抗体检测甘氨酸受体1免疫球蛋白G（GlyR1-IgG）阳性，报告半定量值为1:100，而血清谷氨酸脱羧酶65（GAD65）抗体阴性，支持GlyR-Ab阳性PERM的诊断。患者在联合免疫治疗和对症治疗后初期即显示明显改善。在定期随访中，患者症状逐渐改善。最近一次随访时，复视、面部感觉异常、张口受限和肢体僵硬均已缓解。在不同实验室复查血清显示GlyR1-IgG持续阳性，报告终点滴度为1:100；由于使用了不同的滴定方案，这两个数值结果不能直接比较。建议患者继续口服吗替麦考酚酯500 mg每日两次作为维持治疗。结论：本病例说明了当面部瘙痒和颅-延髓症状先于全身性僵硬出现时，GlyR-Ab阳性PERM的诊断挑战。识别不断演变的刺激诱发肌肉收缩，结合特征性EMG表现和抗体检测，有助于将该表现与感染性颅神经病、破伤风和局部口面部疾病区分开来。

英文摘要

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare and severe phenotype within stiff-person spectrum disorders (SPSD), frequently associated with glycine receptor antibodies (GlyR-Ab). Because typical rigidity and stimulus-sensitive spasms may be absent at disease onset, early diagnosis can be challenging. We report a 52-year-old man who presented with facial pruritus, facial stiffness, limited tongue protrusion, dysphagia, and left lower-limb pain. Early manifestations included diplopia, restricted extraocular movements, dysarthria, restricted mouth opening, involuntary jaw closure resembling trismus, and involuntary tongue biting. Nonspecific oropharyngeal and maxillofacial abnormalities on imaging initially raised concern for infectious multiple cranial neuropathy, tetanus, or orofacial infection; however, antimicrobial therapy and symptomatic treatment with diazepam and pregabalin produced no sustained improvement. The subsequent emergence of neck, truncal, and lower-limb stiffness, gait impairment, perioral hypersensitivity, and stimulus-induced facial muscle contractions prompted reconsideration of SPSD. Needle electromyography (EMG) demonstrated continuous synchronous motor unit activity in agonist and antagonist muscles at rest. Serum antibody testing was positive for glycine receptor 1 immunoglobulin G (GlyR1-IgG), with a reported semiquantitative value of 1:100, whereas serum glutamic acid decarboxylase 65 (GAD65) antibody was negative, supporting the diagnosis of GlyR-Ab-positive PERM. The patient showed marked initial improvement following combined immunotherapy and symptomatic treatment. During regular follow-up, the patient's symptoms progressively improved. At the latest follow-up, diplopia, facial sensory abnormalities, restricted mouth opening, and limb rigidity had resolved. Repeat serum testing at a different laboratory showed persistent GlyR1-IgG positivity, with a reported endpoint titer of 1:100; the two numerical results were not directly comparable because different titration protocols were used. The patient was advised to continue oral mycophenolate mofetil 500 mg twice daily as maintenance therapy. This case illustrates the diagnostic challenges of GlyR-Ab-positive PERM when facial pruritus and cranial-bulbar symptoms precede generalized stiffness. Recognition of evolving stimulus-induced muscle contractions, together with characteristic EMG findings and antibody testing, can help distinguish this presentation from infectious cranial neuropathy, tetanus, and local orofacial disease.