Transforaminal intrathecal delivery of nusinersen for older children and adults with spinal muscular atrophy and complex spinal anatomy: an analysis of 200 consecutive injections

Abstract

BackgroundNusinersen 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.Methods28 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.Results200 (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).ConclusionTransforaminal 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.

Ultrasound‐guided transforaminal approach for nusinersen delivery in adult spinal muscle atrophy patients with challenging access

“…Since several factors may influence the patient's decision for treatment initiation or maintenance, 19 it is important to minimize the factors that cause the patient's discomfort. The only patient that preferred CBCT‐guidance over US‐guidance was the one in whom the prominent vein was inadvertently accessed, an event previously described in CBCT‐guided injections 8 . We acknowledge there may have been a selection bias as the study was set up to assess transforaminal approach.…”

“…Previous studies suggest that 40%‐60% of adult SMA patients present with a difficult spine that prevents the conventional lumbar puncture 2,6,9 . Modalities with ionizing radiation are predominantly used as image guidance options 7‐10 . US‐guidance offers several advantages over broadly used CT or fluroscopic guidance: lower radiation exposure 16 ; lower costs and easier access; more independence, as CBCT is prone to misregistration errors in case of patients' movement; and shorter procedure duration, since no pre‐procedural scanning is needed.…”

Ultra-low radiation dose protocol for CT-guided intrathecal nusinersen injections for patients with spinal muscular atrophy and severe scoliosis

“…The reports on cone-beam CT guidance in terms of nusinersen injection [18,19] present high technical success rate. However, the authors report transforaminal access only which makes it difficult to compare with interlaminar approach.…”

Best Practices for the Orthopaedic Care of Children with Spinal Muscular Atrophy: A Consensus Statement from the European Neuromuscular Centre Standard of Care Orthopaedic Working Group

“…103,108,110,111 Transforaminal and paramedian approaches, lumbar laminectomy, and cervical or suboccipital ports may also be attempted in complex spines. 100,[112][113][114][115][116][117][118][119][120][121][122][123] In some patients, intrathecal administration is still not feasible. 102,124 Considering the difficulties of intrathecal injection posed by spinal instrumentation, preliminary evidence in "skipping" one or more vertebral levels at the thoracolumbar junction has demonstrated increased ease of intrathecal access with no adverse clinical events, loss of correction, or hardware failure at 4 years postoperation 125 (Figure 1).…”