Skip to main content
Top
Published in: Pediatric Radiology 3/2018

01-03-2018 | Original Article

Transforaminal intrathecal delivery of nusinersen using cone-beam computed tomography for children with spinal muscular atrophy and extensive surgical instrumentation: early results of technical success and safety

Authors: John J. Weaver, Niranjana Natarajan, Dennis W. W. Shaw, Susan D. Apkon, Kevin S. H. Koo, Giri M. Shivaram, Eric J. Monroe

Published in: Pediatric Radiology | Issue 3/2018

Login to get access

Abstract

Background

Nusinersen, the only treatment approved by the United States Food and Drug Administration for spinal muscular atrophy (SMA), is delivered intrathecally. Many children with SMA have extensive spinal instrumentation and deformities, often precluding the use of standard approaches for gaining intrathecal access. Furthermore the anatomical distortion that often occurs with rotoscoliosis can complicate the use of fluoroscopic guidance. Compared to fluoroscopy, CT affords superior guidance for complex needle placements. This opens up alternatives to the posterior (interlaminar) technique, including transforaminal and caudal approaches.

Objective

This study describes the early results of technical success, complications and radiation dose of intrathecal delivery of nusinersen using cone-beam CT guidance with two-axis fluoroscopic navigational overlay.

Materials and methods

We conducted a retrospective review of 15 consecutive nusinersen injections performed in four children with SMA and extensive spinal hardware precluding standard posterior lumbar puncture techniques. These children were treated using transforaminal thecal access employing cone-beam CT with navigational overlay. We analyzed results including technical success, complications and total fluoroscopy time.

Results

All procedures were technically successful. No major complications and one minor complication were reported; the minor complication was a post-procedural neuropathic headache that was attributed to procedural positioning and was treated successfully with gabapentin. The average procedural fluoroscopy time and air kerma were 1.9 min and 55.8 mGy, respectively.

Conclusion

Cone-beam CT guidance with two-axis navigational overlay is a safe, effective method for gaining transforaminal intrathecal access in children with spinal abnormalities and hardware precluding the use of standard techniques.
Literature
2.
go back to reference Prior TW, Finanger E (2000) Spinal muscular atrophy. In: Pagon RA, Adam MP, Ardinger HH et al (eds) GeneReviews®. University of Washington, Seattle Prior TW, Finanger E (2000) Spinal muscular atrophy. In: Pagon RA, Adam MP, Ardinger HH et al (eds) GeneReviews®. University of Washington, Seattle
3.
go back to reference Swoboda KJ, Prior TW, Scott CB et al (2005) Natural history of denervation in SMA: relation to age, SMN2 copy number, and function. Ann Neurol 57:704–712CrossRefPubMedPubMedCentral Swoboda KJ, Prior TW, Scott CB et al (2005) Natural history of denervation in SMA: relation to age, SMN2 copy number, and function. Ann Neurol 57:704–712CrossRefPubMedPubMedCentral
4.
go back to reference Hua Y, Sahashi K, Hung G et al (2010) Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model. Genes Dev 24:1634–1644CrossRefPubMedPubMedCentral Hua Y, Sahashi K, Hung G et al (2010) Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model. Genes Dev 24:1634–1644CrossRefPubMedPubMedCentral
5.
6.
go back to reference Chiriboga CA, Swoboda KJ, Darras BT et al (2016) Results from a phase 1 study of nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrophy. Neurology 86:890–897CrossRefPubMedPubMedCentral Chiriboga CA, Swoboda KJ, Darras BT et al (2016) Results from a phase 1 study of nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrophy. Neurology 86:890–897CrossRefPubMedPubMedCentral
7.
go back to reference Finkel R, Kuntz N, Mercuri E et al (2017) Efficacy and safety of nusinersen in infants with spinal muscular atrophy (SMA): final results from the phase 3 ENDEAR study. Eur J Paediatr Neurol 21:e14–e15CrossRef Finkel R, Kuntz N, Mercuri E et al (2017) Efficacy and safety of nusinersen in infants with spinal muscular atrophy (SMA): final results from the phase 3 ENDEAR study. Eur J Paediatr Neurol 21:e14–e15CrossRef
8.
go back to reference Finkel RS, Chiriboga CA, Vajsar J et al (2016) Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet 388:3017–3026CrossRefPubMed Finkel RS, Chiriboga CA, Vajsar J et al (2016) Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet 388:3017–3026CrossRefPubMed
9.
go back to reference Mercuri E, Finkel R, Kirschner J et al (2017) Interim analysis of the phase 3 CHERISH study evaluating nusinersen in patients with later-onset spinal muscular atrophy (SMA): primary and descriptive secondary endpoints. Eur J Paediatr Neurol 21:e15CrossRef Mercuri E, Finkel R, Kirschner J et al (2017) Interim analysis of the phase 3 CHERISH study evaluating nusinersen in patients with later-onset spinal muscular atrophy (SMA): primary and descriptive secondary endpoints. Eur J Paediatr Neurol 21:e15CrossRef
11.
go back to reference Hazra AK, Bhattacharya D, Mukherjee S et al (2016) Ultrasound versus fluoroscopy-guided caudal epidural steroid injection for the treatment of chronic low back pain with radiculopathy: a randomised, controlled clinical trial. Indian J Anaesth 60:388CrossRefPubMedPubMedCentral Hazra AK, Bhattacharya D, Mukherjee S et al (2016) Ultrasound versus fluoroscopy-guided caudal epidural steroid injection for the treatment of chronic low back pain with radiculopathy: a randomised, controlled clinical trial. Indian J Anaesth 60:388CrossRefPubMedPubMedCentral
12.
go back to reference Jones SB, Shaw DW, Jacobson LE (1997) A transsacral approach through the sacral hiatus for myelography. AJR Am J Roentgenol 169:1179–1181CrossRefPubMed Jones SB, Shaw DW, Jacobson LE (1997) A transsacral approach through the sacral hiatus for myelography. AJR Am J Roentgenol 169:1179–1181CrossRefPubMed
13.
go back to reference Andreisek G, Jenni M, Klingler D et al (2013) Access routes and reported decision criteria for lumbar epidural drug injections: a systematic literature review. Skelet Radiol 42:1683–1692CrossRef Andreisek G, Jenni M, Klingler D et al (2013) Access routes and reported decision criteria for lumbar epidural drug injections: a systematic literature review. Skelet Radiol 42:1683–1692CrossRef
14.
go back to reference Abi-Jaoudeh N, Venkatesan AM, Van der Sterren W et al (2015) Clinical experience with cone-beam CT navigation for tumor ablation. J Vasc Interv Radiol 26:214–219CrossRefPubMedPubMedCentral Abi-Jaoudeh N, Venkatesan AM, Van der Sterren W et al (2015) Clinical experience with cone-beam CT navigation for tumor ablation. J Vasc Interv Radiol 26:214–219CrossRefPubMedPubMedCentral
15.
go back to reference Tselikas L, Joskin J, Roquet F et al (2015) Percutaneous bone biopsies: comparison between flat-panel cone-beam CT and CT-scan guidance. Cardiovasc Intervent Radiol 38:167–176CrossRefPubMed Tselikas L, Joskin J, Roquet F et al (2015) Percutaneous bone biopsies: comparison between flat-panel cone-beam CT and CT-scan guidance. Cardiovasc Intervent Radiol 38:167–176CrossRefPubMed
16.
go back to reference McKay T, Ingraham CR, Johnson GE et al (2016) Cone-beam CT with fluoroscopic overlay versus conventional CT guidance for percutaneous abdominopelvic abscess drain placement. J Vasc Interv Radiol 27:52–57CrossRefPubMed McKay T, Ingraham CR, Johnson GE et al (2016) Cone-beam CT with fluoroscopic overlay versus conventional CT guidance for percutaneous abdominopelvic abscess drain placement. J Vasc Interv Radiol 27:52–57CrossRefPubMed
18.
go back to reference Haché M, Swoboda KJ, Sethna N et al (2016) Intrathecal injections in children with spinal muscular atrophy: nusinersen clinical trial experience. J Child Neurol 31:899–906CrossRefPubMedPubMedCentral Haché M, Swoboda KJ, Sethna N et al (2016) Intrathecal injections in children with spinal muscular atrophy: nusinersen clinical trial experience. J Child Neurol 31:899–906CrossRefPubMedPubMedCentral
19.
go back to reference Schwentker EP, Gibson DA (1976) The orthopaedic aspects of spinal muscular atrophy. J Bone Joint Surg 58:32–38CrossRefPubMed Schwentker EP, Gibson DA (1976) The orthopaedic aspects of spinal muscular atrophy. J Bone Joint Surg 58:32–38CrossRefPubMed
20.
go back to reference Phillips DP, Roye DP Jr, Farcy JP et al (1990) Surgical treatment of scoliosis in a spinal muscular atrophy population. Spine 15:942–945CrossRefPubMed Phillips DP, Roye DP Jr, Farcy JP et al (1990) Surgical treatment of scoliosis in a spinal muscular atrophy population. Spine 15:942–945CrossRefPubMed
21.
go back to reference Hong JH, Park EK, Park KB et al (2017) Comparison of clinical efficacy in epidural steroid injections through transforaminal or parasagittal approaches. Korean J Pain 30:220–228CrossRefPubMedPubMedCentral Hong JH, Park EK, Park KB et al (2017) Comparison of clinical efficacy in epidural steroid injections through transforaminal or parasagittal approaches. Korean J Pain 30:220–228CrossRefPubMedPubMedCentral
22.
go back to reference Botwin KP, Gruber RD, Bouchlas CG et al (2000) Complications of fluoroscopically guided transforaminal lumbar epidural injections. Arch Phys Med Rehabil 81:1045–1050CrossRefPubMed Botwin KP, Gruber RD, Bouchlas CG et al (2000) Complications of fluoroscopically guided transforaminal lumbar epidural injections. Arch Phys Med Rehabil 81:1045–1050CrossRefPubMed
23.
go back to reference Lutz GE, Vad VB, Wisneski RJ (1998) Fluoroscopic transforaminal lumbar epidural steroids: an outcome study. Arch Phys Med Rehabil 79:1362–1366CrossRefPubMed Lutz GE, Vad VB, Wisneski RJ (1998) Fluoroscopic transforaminal lumbar epidural steroids: an outcome study. Arch Phys Med Rehabil 79:1362–1366CrossRefPubMed
Metadata
Title
Transforaminal intrathecal delivery of nusinersen using cone-beam computed tomography for children with spinal muscular atrophy and extensive surgical instrumentation: early results of technical success and safety
Authors
John J. Weaver
Niranjana Natarajan
Dennis W. W. Shaw
Susan D. Apkon
Kevin S. H. Koo
Giri M. Shivaram
Eric J. Monroe
Publication date
01-03-2018
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Radiology / Issue 3/2018
Print ISSN: 0301-0449
Electronic ISSN: 1432-1998
DOI
https://doi.org/10.1007/s00247-017-4031-6

Other articles of this Issue 3/2018

Pediatric Radiology 3/2018 Go to the issue