Spinal muscular atrophy (SMA) is a genetic, autosomal recessive neuromuscular disease with an incidence between 1 in 6,000 and 1 in 10,000 live births [1]. Pathogenetically, SMA is caused by a homozygous deletion in the survival motor neuron 1 (SMN1) gene on chromosome 5q13, which leads to insufficient levels of SMN protein [2, 3]. With regard to the onset of clinical symptoms, the achievement of motor milestones, and life expectancy, SMA is divided into different subtypes (SMA types 0–4). Within the 3 main types (SMA types 1–3), SMA type 1 represents the infantile onset and thus the most severe form, while SMA types 2 and 3 are defined as late-onset forms and are characterized by intermediate (SMA type 2) or mild (SMA type 3) types of progression [2]. Regardless of SMA type, typical clinical features include progressive muscle atrophy due to the degeneration of anterior horn cells, early development of joint contractures and scoliosis, and variable bulbar and respiratory weakness [3, 4]. Scoliosis, secondary to progressive axial muscle weakness, has an incidence of 60–90% in patients with SMA types 1 and 2, starting in early childhood and invariably progressing [1, 5–7]. In adult patients, spinal deformities create mechanical disadvantages, affect posture, limit mobility and activities of daily living, and possibly increase respiratory and feeding problems [3].
Nusinersen is an antisense oligonucleotide that modifies pre-mRNA splicing to promote exon 7 inclusion in SMN2 mRNA transcripts, resulting in production of more full-length SMN protein [8, 9], which is clinically effective in infants with type 1 SMA and children or adults with later-onset SMA (types 2 and 3) for improving motor function [10, 11]. This drug cannot pass the blood–brain barrier and, therefore, has to be repeatedly administered intrathecally. For most infants or young children with SMA, intrathecal delivery via a landmark-guided lumbar puncture technique has been shown to be safe, feasible and well tolerated [11]. However, in SMA patients with progressive scoliosis, standard lumbar puncture may be challenging [12–15]. Previous studies showed that computed tomography (CT)- or fluoroscopy-guided techniques could facilitate intrathecal injection of nusinersen in SMA patients with aberrant spinal anatomies [13–15]. However, potential cancer risks existing from associated ionizing radiation of computed CT or fluoroscopy scans – in particular for children, who are more radiosensitive than adults – should not be ignored [16]. The real-time ultrasound-guided technique, with the advantage of avoiding radiation exposure, has been reported to be successfully used by anesthesiologists for central neuraxial block in patients with moderate to severe lumbar scoliosis [17, 18].
In this report, we describe our clinical experience of using the real-time ultrasound-guided technique to deliver nusinersen repeatedly in 3 SMA type 2 and 3 patients with severe scoliosis, through 15 lumbar punctures.