Administration Of Nusinersen In Patients Research Articles

Transverse interlaminar ultrasound-guided C1-C2 puncture for the intrathecal administration of nusinersen in patients with spinal muscular atrophy.

Severe spinal deformities and previous spinal orthopedic instrumentation may result in substantial technical challenges for nusinersen delivery through lumbar puncture in patients with spinal muscular atrophy (SMA). The aim of this paper was to review our experience with ultrasound-guided cervical puncture as an alternative approach for the intrathecal administration of nusinersen. This was a retrospective medical record review of transverse interlaminar ultrasound-guided C1-C2 puncture for nusinersen delivery in SMA patients. The details of puncture, complications, and success rate of the procedure were summarized. There were four patients who received a total of 13 cervical punctures for nusinersen delivery. All procedures were technically successful with no major complications. Full doses of nusinersen were delivered intrathecally. Transverse interlaminar ultrasound-guided C1-C2 puncture is an alternative approach for administering nusinersen if lumbar puncture fails. The success of the technique requires a thorough preprocedural evaluation of cervical spine imaging, sound knowledge of the cervical sonoanatomy and careful manipulation of the needle.

Ultrasound-guided interlaminar approach for nusinersen administration in patients with spinal muscular atrophy with spinal fusion or severe scoliosis

BackgroundIntrathecal injection of medications can be challenging in spinal muscular atrophy (SMA) patients with severe scoliosis or after spine surgery. Here we report our experience with real-time ultrasound (US)-guided intrathecal administration of nusinersen in patients with SMA.MethodsSeven patients (six children and one adult) with either spinal fusion or severe scoliosis were enrolled. We performed intrathecal injections of nusinersen under US guidance. The efficacy and safety of US-guided injection were explored.ResultsFive patients had undergone spinal fusion, while the other two presented severe scoliosis. Success was achieved in 19/20 lumbar punctures (95%), 15 of which were performed through the near-spinous process approach. The intervertebral space with a designated channel was selected for the five postoperative patients, while the interspaces with the smallest rotation angle were chosen for the other two patients with severe scoliosis. In 89.5% (17/19) of the punctures, the number of insertions was no more than two. No major adverse events were observed.ConclusionGiven its safety and efficacy, real-time US guidance is recommended for SMA patients with spine surgery or severe scoliosis, and the near-spinous process view can be used as a interlaminar puncture approach for US guidance.

P.166 Subcutaneous intrathecal catheter and port implants for administration of Nusinersen in patients with Spinal Muscular Atrophy

Background: Until recently, no effective treatment was available for spinal muscular atrophy (SMA). In 2017, Health Canada approved intrathecal Nusinersen a medication that prevents degeneration of the motor neurons in the spinal cord. The administration is intrathecally most commonly via lumbar puncture (LP) to have a direct effect on the motor neurons of the spinal cord.Many older patients with SMA and concomitant spinal deformities present technical challenges to access the thecal sac. Different routes have been described for delivery of the medication. These techniques may require sedation, are associated with radiation exposure, and demand experience personnel. Methods: A new surgical technique has been proposed to overcome these obstacles by combining two Health Canada approved devices: 1) an intrathecal catheter designed for intrathecal baclofen pumps and 2) an implantable subcutaneous port designed for intravascular medication administration Results: We describe the technical nuances and outline the clinical outcomes of six patients with complex spine deformities who have undergone such an implant for administration of Nusinersen. Conclusions: We discuss the benefits of the procedure which includes: 1) administration in the outpatient setting without sedation, 2) avoidance of costly imaging and experienced personnel, and 3) placement of the catheter in the cervicothoracic junction.

P.154 Subcutaneous intrathecal catheter and port implants for administration of Nusinersen in patients with Spinal Muscular Atrophy

Background: Until recently, no effective treatment was available for spinal muscular atrophy (SMA). In 2017, Health Canada approved intrathecal Nusinersen a medication that prevents degeneration of the motor neurons in the spinal cord. The administration is intrathecally most commonly via lumbar puncture (LP) to have a direct effect on the motor neurons of the spinal cord. Many older patients with SMA and concomitant spinal deformities present technical challenges to access the thecal sac. Different routes have been described for delivery of the medication whoever these techniques may require sedation, are associated with radiation exposure, and demand experience personnel. Methods: A new surgical technique has been proposed to overcome these obstacles by combining two Health Canada approved devices: 1) an intrathecal catheter designed for intrathecal baclofen pumps and 2) an implantable subcutaneous port designed for intravascular medication administration Results: We describe the technical nuances and outline the clinical outcomes of six patients with complex spine deformities who have undergone such an implant for administration of Nusinersen. Conclusions: We discuss the benefits of the procedure which includes: 1) administration in the outpatient setting without sedation, 2) avoidance of costly imaging and experienced personnel, and 3) placement of the catheter in the cervicothoracic junction.

Ultrasound assisted lumbar intrathecal administration of nusinersen in adult patients with spinal muscular atrophy: A case series.

Intrathecal nusinersen administration can be challenging in certain adult spinal muscular atrophy (SMA) patients with difficult spinal anatomy who require imaging techniques (fluoroscopy or computed tomography scans) or invasive approaches (catheter placement, laminotomy) to identify the intrathecal space. We used ultrasound (US) assistance to access the lumbar intrathecal space in patients with SMA who experienced previous difficulties or failures with intrathecal dosing. Eighteen adult patients with difficult spines were enrolled. We used US assistance, and we recorded the successful administrations, number of attempts, procedure times, and "patient satisfaction." There were 57 consecutive successful nusinersen spinal administrations in all patients enrolled. In 50% of patients, two or fewer attempts were needed to obtain a successful administration, with four or fewer attempts in 83.3%; only three patients reported more than four attempts because of both severe scoliosis and severe spine rotation (two patients) and obesity (one patient). The mean procedure time was 11.8min (range, 1.7-28.9). Patient satisfaction was 4.97/5 (range, 4-5; median, 5) on Likert scale at 5min and at 72 h. No major adverse events were reported, and two post dural puncture headaches were managed with medical therapy and with complete resolution within 72 h. US assistance seems to be a valid option among treatment choices for intrathecal nusinersen administration in patients with difficult spine. The absence of radiation exposure and the lack of need for intravenous sedation or general anesthesia are additional potential advantages to US assisted administration.

A Systematic Review of Procedural Complications from Transforaminal Lumbar Puncture for Intrathecal Nusinersen Administration in Patients with Spinal Muscular Atrophy.

Spinal muscular atrophy is a progressive neurodegenerative disorder that can be treated with intrathecal antisense oligonucleotide therapy (nusinersen). However, administration is often complicated by posterior spinal fusion and neuromuscular scoliosis, necessitating a transforaminal approach. To assess the safety profile of the transforaminal approach for intrathecal access. Searches of the PubMed, Web of Science, and SCOPUS databases. Thirteen articles were selected based on inclusion of transforaminal access and appropriate clinical information about the procedure. Complications were taken from the included articles and aggregated based on Cardiovascular and Interventional Radiological Society of Europe scale adverse event grading. Total number of complications and grade of complications were analyzed, by year and in total. Selection bias in publication, small patient population size, and variability of the procedure limits the available data. Transforaminal approach is a safe alternative for intrathecal access in patients with spinal muscular atrophy and may be applicable to a larger patient population.

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

PurposeIntrathecal injection of nusinersen is an approved treatment of spinal muscular atrophy (SMA). CT-guided injection is a method of nusinersen administration in patients with severe scoliosis, in whom standard lumbar puncture is not feasible. The injections are repeated every 4 months for life, and accumulated radiation doses absorbed by the patient can increase the risk of cancer. In this study, we present the results of CT-guided intrathecal nusinersen injections with an ultra-low radiation dose protocol.MethodsEighteen patients (15 adults and three children) in whom standard lumbar puncture was not feasible due to severe scoliosis or spinal stabilization were included in this retrospective study. The first 23 injections were performed with a standard radiation dose protocol and the next 42 injections with an ultra-low-dose protocol. The radiation doses, measured as total dose length product (DLP), were acquired and compared between the protocols.ResultsInjections were successful in 100% of patients with both ultra-low-dose and standard protocols. The radiation dose, measured as DLP, was 111.2–1100.7 (Me = 248.1) mGy*cm for the standard protocol. For the ultra-low-dose protocol, the dose range was 5.0–54.4 (Me = 26.7) mGy*cm, which was significantly lower than with the standard protocol (p < 0.001, η2 = 0.67).ConclusionRadiation doses can be significantly decreased in the CT-guided injection of nusinersen. The proposed protocol allows for effective CT-guided intrathecal nusinersen administration in patients with SMA and severe scoliosis.

P.373Longitudinal changes in electrophysiological findings caused by nusinersen administration in patients with spinal muscular atrophy type 2 or type 3

The aim of this study was to determine changes in electrophysiological findings caused by nusinersen administration in patients with spinal muscular atrophy (SMA) and to verify whether an electrophysiological study can reflect the changes in the neural system induced by nusinersen. Data for 12 SMA patients (7 patients with SMA type 2 and 5 patients with SMA type 3) administered nusinersen >3 times were retrospectively reviewed. The median age of first nusinersen administration was 8.5 years and 7 patients were male. We performed nerve conduction studies and repetitive nerve stimulation (RNS) after every nusinersen administration and compared the findings to those before the administration. The average median F wave-occurrence (FO) was 35% before nusinersen treatment and 60% after the third administration, a significant difference. The average ulnar FO was 45% before nusinersen treatment and 71% after the third administration, a significant difference. The tibial FO could not be evaluated in 8 patients due to low compound muscle action potentials before nusinersen administration. However, among them, four patients could be evaluated after the treatment. On median RNS, 3 and 2 patients showed decrement >10% and >5%, respectively; three of them showed no decrement after the third administration. Ulnar RNS revealed decrement in 9 of 11 patients who underwent ulnar RNS. Median motor unit number estimation (MUNE) values increased statistically significantly by 60% on average by the fourth administration. All patients whose median MUNE values decreased or did not change after the treatment were more than 10 years old. An FO increase and an increase in MUNE values suggest a functional improvement of anterior horn cells. A decrement and restoration on RNS may indicate an immature neuromuscular junction resulting from motor nerve terminal sprouting induced by nusinersen. An electrophysiological study can reflect the changes in the neural system precipitated by nusinersen.