Surgical success of subcutaneous systems for intrathecal nusinersen delivery in spinal muscular atrophy: A systematic review and meta-analysis

Background

The intrathecal administration of nusinersen to treat spinal muscular atrophy (SMA) has demonstrated therapeutic effect, however, repeat lumbar punctures confer multiple disadvantages. As such, subcutaneous systems have been described to provide an alternative, less invasive strategy for repeat administration. Correspondingly this study aimed to aggregate metadata to better define the surgical success of these subcutaneous systems.

Methods

Searches of multiple electronic databases from inception to March 2025 were conducted following PRISMA guidelines. Articles were screened against pre-specified criteria. Quantitative outcomes were pooled by random-effects meta-analyses where possible.

Results

There were 8 studies describing 74 SMA patients that were managed with a subcutaneous system for intrathecal nusinersen. No official system currently exists for this purpose, and all studies reported off-label use of either an intravascular port (5 of 8 studies) or reservoir system (3 of 8 studies) as the subcutaneous port. These ports were located mostly in the lateral flank (5 of 8 studies). In terms of intrathecal access, a hemilaminotomy was used universally in most studies (6 of 8 studies), and access was obtained most commonly in the thoracolumbar region (3 of 8 studies). A total of 22 individual adverse events were reported amongst the cohort, the most common being cerebrospinal fluid leak needing intervention (7/74, 9 %). The pooled estimate by meta-analysis indicated an overall weighted rate of adverse events to be 27 % (95 % CI 16–40 %). Eight patients required revision surgery, with a pooled revision surgery rate estimate of 9 % (95 % CI 2–19 %).

Conclusions

Subcutaneous systems can be used in the setting of SMA for repeat nusinersen administration. There exists no consensus system or surgical approach currently, with multiple systems, port types, port location, intrathecal access techniques and intrathecal access locations reported. Future multidisciplinary efforts are needed to elevate the concept of subcutaneous delivery systems for SMA towards convention.