Intrathecal nusinersen administration in adult spinal muscular atrophy patients with complex spinal anatomy

Abstract

Background: Intrathecal administration of nusinersen in adult spinal muscular atrophy (SMA) patients presents challenges owing to severe scoliosis and previous spinal surgery with metal implantation. In patients with a complex spinal situation, the potential risks of the intrathecal administration may lead to delayed treatment initiation.

Methods: In this study, we analyzed 53 CT-guided lumbar punctures of 11 adult nonambulatory SMA type 2 and 3 patients. All patients had scoliosis and six patients had previously undergone metal implantation.

Results: Drug administration was successful in 100% of the patients and none of the patients opted for treatment discontinuation. Complete osseous fusion precluded conventional posterior interlaminar access in eight lumbar punctures in four patients, which required alternative routes including transforaminal punctures and translaminar drilling. Median duration of all lumbar punctures was 9 min and median radiation exposure was 100 mGy* cm. The most common adverse event was post-lumbar puncture syndrome that occurred in five lumbar punctures (9.4%).

Conclusions: Our data demonstrate that nusinersen can be successfully, safely, and rapidly administered in adult SMA patients with complex spinal conditions and suggest the translaminar drilling technique as an alternative delivery route. Therefore, intrathecal nusinersen treatment should not be withheld from patients because of severe spine deformities, however, drug efficacy in adult SMA patients needs to be investigated in further studies.

Keywords: computed tomography; radiation exposure; scoliosis; transforaminal; translaminar drill.

Figure 1.

Illustration of two consecutive nusinersen injections in a 25-year-old woman with SMA type 2. Owing to complete osseous fusion of the dorsal parts of the lumbar spine, there was initially no access except for the transforaminal route (a), which was accessed by a 20 G spinal needle (*). For anatomical reasons, the ventral part of the neural foramen was targeted in this patient. Because this puncture caused lumbar pain and post-puncture headache, in the next session (b) a dorsal 11 G (**) cavity was drilled transosseously at level L2/3. Coaxial to the osseous needle, an 18 G spinal needle (*) was advanced into the spinal canal. At the next intervention, the new osseous canal was used for easy access using a conventional 20 G spinal needle (not shown). SG, spinal ganglion.

Figure 2.

CT imaging showing a 45-year-old SMA type 2 patient with complete dorsal fusion of the bony spine after dorsal stabilization (a, b). During the first intervention, a bone canal was drilled at level L3/4 (c)–(e), through which a spinal needle could be inserted during the first and subsequent interventions. A 3 mm bone cylinder was removed during the first procedure (f).

Figure 3.

Radiation exposure for first to last CT-guided intervention during intrathecal treatment with nusinersen, shown as a boxplot with data points. Given numbers (n) refer to SMA patients included in the subgroups of first to last intervention.