Spinalmuscular atrophy (SMA) is a genetic disease affecting the second motor neuron, causing progressive muscle atrophy and weakness due to decreased expression of the survival motor neuron. Different subtypes exist, type 2 is one of the most frequent ones.
The disorder is caused by a genetic defect in the SMN1 gene, which encodes SMN, a protein widely expressed in all eukaryotic cells (that is, cells with nuclei, including human cells) and necessary for survival of motor neurons. Lower levels of the protein results in loss of function of neuronal cells in the anterior horn of the spinal cord and subsequent system-wide atrophy of skeletal muscles.
Spinal muscular atrophy manifests in various degrees of severity, which all have in common progressive muscle wasting and mobility impairment. Proximal muscles, arm and leg muscles that are closer to the torso and respiratory muscles are affected first. Other body systems may be affected as well, particularly in early-onset forms of the disorder. SMA is the most common genetic cause of infant death.
Spinal muscular atrophy is an inherited disorder and is passed on in an autosomal recessive manner (see video explanation of autosomal recessive inheritance). In December 2016, nusinersen became the first approved drug to treat SMA while several other compounds remain in clinical trials.
These patients show a high incidence of scoliosis requiring surgery. In 2016 and 2017, the Federal Drug Administration and the European Medical Agency approved nusinersen for all types of SMA. It is a splicing modifier that enhances the expression of survival motor neuron and it has to be administered intrathecally. In patients with profound scoliosis, intrathecal administration can be challenging. Here, we present our experience with the implantation of an intrathecal port in a patient with SMA type 2.
A 16-year-old girl with SMA type 2 was referred for intrathecal nusinersen therapy. Because of severe scoliosis, spondylodesis of the segments TH7-S1 was performed at 14 years of age. The first two loading doses were given by spinal tap under sedation and computed tomography guidance, but we were unable to administer the following dose because of severe scoliotic spinal deformation. To ensure further drug therapy, an intrathecal port catheter (Celsite® Safety; Braun, Germany) was implanted via microsurgical hemilaminectomy L4. Further intrathecal nusinersen administration was uneventful.
They conclude that the implantation of an intrathecal port system in patients with SMA and profound scoliosis is a safe and feasible procedure and allows the administration of nusinersen while reducing the need for sedation and exposure to radiation 1).