Introduction: Spinal muscular atrophy (SMA) is a debilitating neuromuscular disorder caused by biallelic deletion of the SMN1 gene. Nusinersen, an antisense oligonucleotide delivered intrathecally, binds to the pre-mRNA of SMN1’s pseudogene, SMN2, to prevent exon skipping and produce functional SMN protein to compensate for the deficiency caused by SMN1 deletion. Case Presentation: We reviewed 15 cerebrospinal fluid (CSF) cytology specimens from 8 patients receiving nusinersen for SMA. Macrophages with peculiar inclusions (“nusinophages”) were seen in 8 specimens from 4 of the patients: 1 infant and 3 children with SMA type 1. This finding has only previously been reported in adults with SMA types 2 and 3 and in 2 infants with SMA type 1. Discussion/Conclusion: Specimens containing nusinophages had a significantly higher proportion of macrophages and lower proportion of lymphocytes than those in which nusinophages were not detected. The macrophage inclusions do not represent iron or microorganisms and instead are composed, at least in part, of glycosaminoglycans. Because CSF is a common specimen type, cytotechnologists and cytopathologists need to be aware of these inclusions, so they do not interpret them erroneously as evidence of infection or hemorrhage, especially in light of the fact that oligonucleotide therapy has been approved for a variety of conditions and is currently under investigation for intrathecal delivery in several other neurodegenerative disorders.
Acta Cytologica

中文翻译：

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接受鞘内 Nusinersen (SPINRAZA®) 治疗脊髓性肌萎缩症的儿科患者脑脊液巨噬细胞包涵体的细胞化学特征

简介：脊髓性肌萎缩症 (SMA) 是一种由SMN1基因双等位基因缺失引起的使人衰弱的神经肌肉疾病。Nusinersen 是一种鞘内递送的反义寡核苷酸，它与SMN1的假基因SMN2的前 mRNA 结合，以防止外显子跳跃并产生功能性 SMN 蛋白以弥补SMN1缺失引起的缺陷。案例介绍：我们审查了来自 8 名接受 nusinersen 的 SMA 患者的 15 份脑脊液 (CSF) 细胞学标本。在来自 4 名患者的 8 个样本中发现了具有特殊包涵体的巨噬细胞（“nusinophages”）：1 名婴儿和 3 名儿童患有 1 型 SMA。这一发现以前仅在患有 2 型和 3 型 SMA 的成人以及 2 名患有 SMA 的婴儿中报道过。 SMA 类型 1。讨论/结论：与未检测到噬菌体的标本相比，含有噬菌体的标本具有显着更高比例的巨噬细胞和更低的淋巴细胞比例。巨噬细胞内含物不代表铁或微生物，而是至少部分由糖胺聚糖组成。由于 CSF 是一种常见的标本类型，因此细胞技术人员和细胞病理学家需要了解这些内含物，因此他们不会将它们错误地解释为感染或出血的证据，尤其是考虑到寡核苷酸疗法已被批准用于多种疾病的事实目前正在研究其他几种神经退行性疾病的鞘内给药。
细胞学学报