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. 2018 Oct 5:11:1756286418803246.
doi: 10.1177/1756286418803246. eCollection 2018.

Feasibility and safety of intrathecal treatment with nusinersen in adult patients with spinal muscular atrophy

Benjamin Stolte  1 , Andreas Totzeck  1 , Kathrin Kizina  1 , Saskia Bolz  1 , Lena Pietruck  1 , Christoph Mönninghoff  2 , Nika Guberina  2 , Denise Oldenburg  2 , Michael Forsting  2 , Christoph Kleinschnitz  1 , Tim Hagenacker  3
Affiliations

Feasibility and safety of intrathecal treatment with nusinersen in adult patients with spinal muscular atrophy

Benjamin Stolte et al. Ther Adv Neurol Disord. .

Abstract

Background: Nusinersen is an intrathecally administered antisense oligonucleotide (ASO) and the first approved drug for the treatment of spinal muscular atrophy (SMA). However, progressive neuromyopathic scoliosis and the presence of spondylodesis can impede lumbar punctures in SMA patients. Our aim was to assess the feasibility and safety of the treatment in adults with SMA.

Methods: For the intrathecal administration of nusinersen, we performed conventional, fluoroscopy-assisted and computer tomography (CT)-guided lumbar punctures in adult patients with type 2 and type 3 SMA. We documented any reported adverse events and performed blood tests.

Results: We treated a total of 28 adult SMA patients (9 patients with SMA type 2 and 19 patients with SMA type 3) aged between 18-61 years with nusinersen. The mean Revised Upper Limb Module (RULM) score at baseline in SMA type 2 and SMA type 3 patients was 9.9 ± 4.6 and 29.5 ± 8.5, respectively. The mean Hammersmith Functional Motor Scale Expanded (HFMSE) score at baseline was 3.1 ± 2.5 and 31.2 ± 18.1, respectively. Half of the SMA type 3 patients were ambulatory at treatment onset. In total, we performed 122 lumbar punctures with 120 successful intrathecal administrations of nusinersen. Lumbar punctures were well tolerated, and no serious adverse events occurred.

Conclusions: Our data demonstrate the feasibility and tolerability of intrathecal treatment with nusinersen in adults with SMA type 2 and type 3. However, treatment can be medically and logistically challenging, particularly in patients with SMA type 2 and in patients with spondylodesis.

Keywords: SMA; computer tomography; fluoroscopy; lumbar puncture; scoliosis; spondylodesis.

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Conflict of interest statement

Conflict of interest statement: BS received travel reimbursement from Biogen. CK received travel reimbursement and speaker honoraria from Biogen. TH received travel reimbursement from Biogen and speaker honoraria from Novartis and Biogen. AT, KK, SB, LP, NG, CM and MF declared no conflicts of interest.

Figures

Figure 1.
Figure 1.
Three-dimensional computed tomography reconstruction in a volume rendering technique of a 44-year-old patient with SMA type 2 demonstrates the torsion of the scoliotic thoracolumbar spine, which complicates lumbar puncture for the intrathecal administration of nusinersen. SMA, spinal muscular atrophy.
Figure 2(a).
Figure 2(a).
Lateral tomogram of a 29-year-old patient with SMA type 2 with implanted spondylodesis and femoral head replacement. The scoliosis, the spondylodesis, and the reduced visibility of the demineralised vertebral bodies complicate the lumbar puncture without computed tomographic guidance. SMA, spinal muscular atrophy. Figure 2(b). Axial computed tomography scan of the same patient with intrathecal needle placement at the level of L 4/5. Despite the use of iterative metal artefact reduction, the contrast between the spinal canal and the spinous processes is challenging for intrathecal needle placement.
See this image and copyright information in PMC

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