Wang Xiaoli, Zhang Xinbo, Yuan Na, Liu Yonghong
Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Ann Clin Transl Neurol. 2025 Mar;12(3):666-669. doi: 10.1002/acn3.52284. Epub 2024 Dec 27.
To explore the efficacy of ofatumumab in new onset narcolepsy type 1 following SARS-CoV-2 infection.
We present a 9-year-old girl who experienced new onset narcolepsy type 1 following SARS-CoV-2 infection. Polysomnography (PSG) followed by a daytime multiple sleep latency test (MSLT) was under taken after admission. A lumbar puncture was performed to evaluate the CSF orexin-A level. We assessed the CSF hypocretin-1 concentration utilizing the RIA kit from Phoenix Pharmaceuticals Inc. HLA typing was performed. Furthermore, we treated the patient with subcutaneous injections of ofatumumab, and followed her for nearly six-month. The CSF orexin-A level, CD19+ and total B cell population were measured before and after treatment.
The girl had experienced SARS-CoV-2 infection 4 months before presentation. After that, she started to experience excessive daytime sleepiness and cataplexy. She also began to experience nightmares and violent behaviors during her nocturnal sleep, which were not present before her SARS-CoV-2 infection. At the same time, she developed obesity and exhibited psychiatric symptoms such as agitation, anxiety, and aggression. MSLT showed a mean sleep latency of 2.7 min, and 5 times sleep onset REM periods. The CSF orexin-A level was pathologically low at 34.06 pg/mL, and she tested positive for HLA-DQB1*06:02. Consequently, a diagnosis of narcolepsy type 1 was confirmed. Before and after treatment with subcutaneous injections of ofatumumab, the CD19+ and total B cell population before treatment and after 1 months showed a significant reduction from 11% and 296 cells per microliter to 0.56% and 11 cells per microliter, respectively. Within a week following ofatumumab therapy, there was a marked improvement in both excessive daytime sleepiness and cataplexy. Notably, her cataplexy was almost entirely resolved following ofatumumab therapy. Her condition remained stable throughout the 9-month follow-up period. She could normally attend school.
The efficacy of ofatumumab in this case provides additional support for an autoimmune etiology in narcolepsy with cataplexy, highlighting the potential involvement of B-cells in its pathophysiology. This understanding will aid in the development of specific immunotherapeutic strategies for early implementation upon disease onset.
探讨奥法妥木单抗对新型冠状病毒2（SARS-CoV-2）感染后新发1型发作性睡病的疗效。
我们报告一名9岁女孩，她在感染SARS-CoV-2后出现了新发1型发作性睡病。入院后进行了多导睡眠图（PSG）检查，随后进行了白天多次睡眠潜伏期试验（MSLT）。进行腰椎穿刺以评估脑脊液食欲素-A水平。我们使用Phoenix Pharmaceuticals Inc.的放射免疫分析试剂盒评估脑脊液下丘脑分泌素-1浓度。进行了HLA分型。此外，我们对患者进行皮下注射奥法妥木单抗治疗，并对她进行了近6个月的随访。在治疗前后测量脑脊液食欲素-A水平、CD19+和总B细胞群体。
该女孩在就诊前4个月感染了SARS-CoV-2。此后，她开始出现白天过度嗜睡和猝倒。她还开始在夜间睡眠中经历噩梦和暴力行为，这些在她感染SARS-CoV-2之前并不存在。同时，她出现了肥胖，并表现出如烦躁、焦虑和攻击性等精神症状。MSLT显示平均睡眠潜伏期为2.7分钟，有5次入睡时快速眼动期。脑脊液食欲素-A水平病理性降低，为34.06 pg/mL，她的HLA-DQB1*06:02检测呈阳性。因此，确诊为1型发作性睡病。在皮下注射奥法妥木单抗治疗前后，治疗前和治疗1个月后的CD19+和总B细胞群体分别从11%和每微升296个细胞显著减少至0.56%和每微升11个细胞。在奥法妥木单抗治疗后的一周内，白天过度嗜睡和猝倒均有明显改善。值得注意的是，奥法妥木单抗治疗后她的猝倒几乎完全缓解。在9个月的随访期内她的病情保持稳定。她能够正常上学。
奥法妥木单抗在该病例中的疗效为伴有猝倒的发作性睡病的自身免疫病因提供了额外支持，突出了B细胞在其病理生理学中的潜在作用。这种认识将有助于开发特定的免疫治疗策略，以便在疾病发作时尽早实施。
