DataSheet_1_Case report: Excessive daytime sleepiness as a presenting manifestation of autoimmune glial fibrillary acidic protein astrocytopathy.pdf

Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a recently discovered autoimmune inflammatory disease of the central nervous system. It presents with a variety of clinical symptoms, including fever, seizures, psychiatric symptoms, limber weakness, and sensory symptoms. However, the symptoms of sleep disorders have not been sufficiently addressed. Here, we report a case of GFAP-A in which the patient complained of excessive daytime sleepiness and an excessive need for sleep. Our patient was a 58-year-old male who experienced excessive daytime sleepiness for 50 days following SARS-CoV-2 infection. He was diagnosed with coronavirus disease 2019 on June 1st. On the 7th of June, he experienced excessive daytime sleepiness, nausea, reduced food intake, lower limb weakness, and dysuria. Subsequently, his sleepiness significantly deteriorated on July 21st. Five months prior, the patient underwent laparoscopic partial right nephrectomy for clear-cell renal cell carcinoma. Brain MRI revealed abnormal hyperintense lesions in the pontine brain and around the mesencephalic aqueduct on T2 and T2-fluid attenuated inversion recovery (T2-FLAIR) sequences However, these lesions did not exhibit any pathological enhancement. Spinal cord MRI revealed lesions in the C6–C7 and T2–T3 segments on the T2 sequence. His Epworth Sleepiness Scale (ESS) score was 16 (reference range, <10), and 24-hour polysomnography supported the diagnosis of rapid-eye-movement sleep disorder and severe sleep apnea-hypopnea syndrome. Glial fibrillary acidic protein IgG antibodies were detected in the cerebrospinal fluid (1:32, cell-based assay) but not in the serum. The level of hypocretin in the cerebrospinal fluid was 29.92 pg/mL (reference range ≥110 pg/mL), suggesting narcolepsy type 1. After treatment with corticosteroids for approximately 1 month, the patient showed considerable clinical and radiological improvement, as well as an increase in hypocretin levels. Although repeated polysomnography and multiple sleep latency tests suggested narcolepsy, his ESS score decreased to 8. Our findings broaden the range of clinical manifestations associated with GFAP-A, thereby enhancing diagnostic and therapeutic strategies for this disease. Additionally, our results indicate a potential common autoimmune mechanism involving GFAP-A and orexin system dysregulation, warranting further investigation.

胶质纤维酸性蛋白自身免疫性星形细胞病（Autoimmune glial fibrillary acidic protein astrocytopathy, GFAP-A）是一种新近发现的中枢神经系统自身免疫炎性疾病。该疾病可表现为多种临床症状，包括发热、癫痫发作、精神症状、肢体无力及感觉障碍，但睡眠相关症状尚未得到充分重视。本文报告1例以日间过度嗜睡及睡眠需求过量为主要主诉的GFAP-A患者。该患者为58岁男性，在感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）后出现长达50天的日间过度嗜睡。患者于6月1日被确诊为新型冠状病毒肺炎（COVID-19）。6月7日，患者出现日间过度嗜睡、恶心、进食减少、下肢无力及排尿困难。随后，其嗜睡症状于7月21日显著加重。5个月前，该患者因透明细胞肾细胞癌接受了腹腔镜右肾部分切除术。脑部磁共振成像（Magnetic Resonance Imaging, MRI）结果显示，桥脑及中脑导水管周围区域在T2加权序列与T2液体衰减反转恢复（T2-FLAIR）序列上可见异常高信号病灶，但上述病灶无病理性强化。脊髓磁共振成像显示，T2序列下C6-C7及T2-T3节段存在病灶。患者的爱泼沃斯嗜睡量表（Epworth Sleepiness Scale, ESS）评分为16分（参考范围：<10分）；24小时多导睡眠监测（polysomnography, PSG）结果支持快速眼动睡眠行为障碍与重度睡眠呼吸暂停低通气综合征的诊断。脑脊液中检测到胶质纤维酸性蛋白IgG抗体（1:32，细胞测定法），但血清中未检出该抗体。脑脊液食欲素（hypocretin）水平为29.92 pg/mL（参考范围≥110 pg/mL），提示1型发作性睡病。经糖皮质激素治疗约1个月后，患者的临床症状与影像学表现均得到显著改善，脑脊液食欲素水平也有所升高。尽管复查多导睡眠监测及多次睡眠潜伏期测试（multiple sleep latency test, MSLT）仍提示发作性睡病，但患者的ESS评分已降至8分。本研究结果拓宽了GFAP-A相关临床表现的谱系，为该疾病的诊疗策略提供了新的参考依据。此外，本研究提示GFAP-A与食欲素系统失调可能存在共同的自身免疫机制，有待进一步深入研究。