Background Nusinersen is the only approved treatment for all spinal muscular atrophy (SMA) subtypes and is delivered intrathecally. Distorted spinal anatomy and instrumentation preclude standard approaches for intrathecal access, necessitating alternative techniques for delivery. The purpose of this study is to report technical success and adverse events of transforaminal intrathecal delivery of nusinersen.
Methods 28 patients, mean age 24.1±9.8 years (range 10.0–51.0 years), with intermediate or late onset SMA, underwent a combined 200 transforaminal nusinersen injections. All patients had osseous fusion or spinal instrumentation precluding standard posterior access routes. Patients who underwent nusinersen injections using a technique other than transforaminal lumbar puncture (n=113) were excluded. Technical success, adverse events (AEs) and radiation exposure were recorded.
Results 200 (100%) procedures were technically successful; 6 (3%) required a second level of attempt for access. 187 (93.5%) interventions were completed using cone beam computed tomography (CBCT) with two-axis fluoroscopic navigational overlay. 13 (6.5%) procedures were performed with fluoroscopic-guidance only at subsequent sessions. There were 8 (4.0%) mild AEs and 2 (0.5%) severe AEs; one patient received antibiotics for possible traversal of the large bowel but did not develop meningitis, and one patient developed aseptic meningitis. Mean air kerma was 74.5±161.3 mGy (range 5.2–1693.0 mGy).
Conclusion Transforaminal intrathecal delivery of nusinersen is feasible and safe for gaining access in patients with distorted spinal anatomy. The use of CBCT delineates anatomy and optimizes needle trajectory during the initial encounter, and may be used selectively for subsequent procedures.
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Contributors All authors met the criteria for authorship. JJW, JFBC, and EJM analyzed and interpreted the data, and wrote the article, and thereby take responsibility for this work. DKH, JFBC and EJM conceived the study and participated in its design and coordination. SV, DSS, NN, NR, JR, KSHK, GMS, AT, SA assisted with manuscript composition. Conception and design of this work were discussed with all of the authors. All authors agreed to publish this work and critically reviewed the article.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests EJM discloses scientific advisory and speaking for Biogen, Inc. NN receives research support for studies for Biogen, Inc.
Patient consent for publication Parental/guardian consent obtained.
Ethics approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study did not receive funding. Written consent was obtained for anonymized pictures displayed in Figure 1. Informed consent for data was waived from all individual participants included in the study. The study was approved by the institutional ethics committee at Seattle Children’s Hospital (institutional registration numbers: IRB00000277, IRB00009311; study number: STUDY00002336).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.