Display options
Cite
Schafernak KT, Jacobsen JR, Hernandez D, et al. Cytochemical Characterization of Cerebrospinal Fluid Macrophage Inclusions in Pediatric Patients Receiving Intrathecal Nusinersen (SPINRAZA®) for Spinal Muscular Atrophy. Acta Cytol. 2021;66(1):79-84doi: 10.1159/000518005.
Schafernak, K. T., Jacobsen, J. R., Hernandez, D., Kaye, R. D., & Perez, S. E. (2022). Cytochemical Characterization of Cerebrospinal Fluid Macrophage Inclusions in Pediatric Patients Receiving Intrathecal Nusinersen (SPINRAZA®) for Spinal Muscular Atrophy. Acta cytologica, 66(1), 79-84. https://doi.org/10.1159/000518005
Schafernak, Kristian T, et al. "Cytochemical Characterization of Cerebrospinal Fluid Macrophage Inclusions in Pediatric Patients Receiving Intrathecal Nusinersen (SPINRAZA®) for Spinal Muscular Atrophy." Acta cytologica vol. 66,1 (2022): 79-84. doi: https://doi.org/10.1159/000518005
Schafernak KT, Jacobsen JR, Hernandez D, Kaye RD, Perez SE. Cytochemical Characterization of Cerebrospinal Fluid Macrophage Inclusions in Pediatric Patients Receiving Intrathecal Nusinersen (SPINRAZA®) for Spinal Muscular Atrophy. Acta Cytol. 2022;66(1):79-84. doi: 10.1159/000518005. Epub 2021 Aug 17. PMID: 34515035.
Copy Download .nbib Format: NLM
Share it on

Acta Cytol. 2022;66(1):79-84. doi: 10.1159/000518005. Epub 2021 Aug 17.

Cytochemical Characterization of Cerebrospinal Fluid Macrophage Inclusions in Pediatric Patients Receiving Intrathecal Nusinersen (SPINRAZA®) for Spinal Muscular Atrophy.

Acta cytologica

Kristian T Schafernak, Jeffrey R Jacobsen, Dulce Hernandez, Robin D Kaye, Sylvia E Perez

Affiliations

  1. Department of Pathology and Laboratory Medicine, Phoenix Children's Hospital, Phoenix, Arizona, USA.
  2. Department of Radiology, Phoenix Children's Hospital, Phoenix, Arizona, USA.
  3. Department of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona, USA.

PMID: 34515035 DOI: 10.1159/000518005

Abstract

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.

© 2021 S. Karger AG, Basel.

Keywords: Cerebrospinal fluid; Cytology; Macrophage; Nusinersen; Spinal muscular atrophy

Publication Types