nusinersen and Scoliosis

This study investigated the efficacy and safety of nusinersen, an antisense oligonucleotide, in patients with spinal muscular atrophy (SMA) types II (OMIM: 253,550) or III (OMIM: 253,400), including those with severe scoliosis or requiring respiratory support via mechanical ventilation.. Data from 40 patients with genetically confirmed SMA who were treated with nusinersen at our institute from March 2019 to April 2022 were retrospectively analyzed. Of these, 30 patients with an age of onset < 3 years and not on permanent ventilation were selected. Clinical and genetic characteristics were investigated, and motor function was evaluated based on the Hammersmith Functional Motor Scale-Expanded (HFMSE) score.. The mean age of symptom onset was 1.2 years. Most patients were diagnosed with SMA type II (27/30, 90%). Nusinersen was administered via computed tomography-guided or direct intrathecal injection in 87% (26/30) and 13% (4/30) of the patients, respectively. At the 6-, 14-, 22-, and 26-month follow-ups, 72%, 71%, 88%, and 86% of patients showed motor improvement, respectively, with mean changes in HFMSE scores of 2.10, 2.88, 4.21, and 5.29, respectively. Multivariable analysis showed that the use of noninvasive ventilation was associated with poorer outcomes of motor function.. Patients with SMA type II or III who received nusinersen treatment showed significant improvement in motor function. A longer treatment duration led to a higher number of patients with improved motor function. No significant side effects of nusinersen were observed. Patients with SMA, even those with severe scoliosis or on respiratory support, can be safely treated using nusinersen.

Topics: Child, Preschool; Humans; Infant; Republic of Korea; Retrospective Studies; Scoliosis; Spinal Muscular Atrophies of Childhood

Real-world data have shown variability in treatment responses to nusinersen in spinal muscular atrophy (SMA). We investigated whether the magnitude of muscle impairment assessed by magnetic resonance imaging (MRI) at baseline can predict the treatment response.. We retrospectively assessed the clinical data in relevance to the thigh and pelvic MRI taken before the nusinersen treatment. A total of 16 patients with SMA types 2 and 3 (age = mean [SD]; 9.2 [4.6] year) receiving nusinersen treatment were enrolled. The T1-weighted MRI images of the pelvis and thigh were scored for muscle fatty infiltration and atrophy. The minimally clinically important difference (MCID) was considered as gaining at least 3 points of Hammersmith Functional Motor Scale-Expanded (HFMSE) from baseline.. Of these 16 individuals, 14 had been treated for at least 15 months with baseline data. At 15 months, seven individuals obtained MCID in HFMSE. Baseline muscle MRI score could not differentiate the two groups; however, individuals who obtained MCID had significantly less severe scoliosis. In addition, there was a significant and negative relationship between baseline MRI score and the change of score in HFMSE after 15 months of treatment. Further, baseline Cobb angle along with MRI score also indicated the correlation to the degree of change in motor function.. The degree of muscle damage may confer the variability in response to nusinersen in SMA types 2 and 3. Muscle MRI score along with the severity of scoliosis assessed at baseline may help to predict the motor function change.

Topics: Humans; Magnetic Resonance Imaging; Muscles; Muscular Atrophy, Spinal; Retrospective Studies; Scoliosis; Spinal Muscular Atrophies of Childhood

Intrathecal nusinersen administration, a fundamental step in the treatment of spinal muscular atrophy, is challenging in children.. This retrospective monocentric analysis of prospectively collected data evaluated the feasibility of needleless general anesthesia exclusively with sevoflurane, without imaging guidance, for children undergoing nusinersen administration in a 24-month period.. Clinical data included demographics, type of spinal muscular atrophy, presence and severity of scoliosis. Primary outcome was defined by the number of predefined sentinel adverse events related to anesthesia. Secondary outcomes were assessed by duration of the procedure, number of lumbar puncture attempts, and number of failures. Other measures included number and type of moderate, minor and minimal adverse events, as well as number and type of puncture-related adverse events.. 116 patients (mean age: 8.7 (SD 6.9) years; with scoliosis: 49.1%) underwent 250 lumbar punctures; two cases of prolonged desaturation, considered as sentinel adverse events, (0.8%) were recorded during anesthesia (primary outcome). None of the patients underwent orotracheal intubation nor required an unplanned admission in the Pediatric Intensive Care Unit. No patient required an unplanned or prolonged hospitalization after the procedure. Mean number of puncture attempts was 1.6 (SD 1.3), and mean duration of the procedure was 14.1 (SD 8.3) minutes. No failure in the drug administration occurred (secondary outcomes).. In this single-center experience, needleless general anesthesia with inhaled sevoflurane without imaging guidance has been shown to be feasible for children with spinal muscular atrophy undergoing lumbar puncture for nusinersen administration.

Topics: Anesthesia, General; Child; Humans; Injections, Spinal; Muscular Atrophy, Spinal; Retrospective Studies; Scoliosis; Sevoflurane

Intrathecal 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.. Seven 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.. Five 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.. Given 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.

Topics: Adult; Child; Humans; Muscular Atrophy, Spinal; Scoliosis; Spinal Fusion; Ultrasonography, Interventional

Emergence of new treatments for spinal muscular atrophy type 1 (SMA1) has led to dramatic improvements in respiratory failure and survival. However, these "treated" patients sustain major problems in other organ systems, which may directly or indirectly affect their respiratory function. We observed three main nonrespiratory manifestations in these patients comprised of facial deformities, feeding problems, and spinal deformities.. To investigate these three main sequelae in nusinersen-treated SMA1 patients.. Data on nusinersen-treated SMA1 patients were prospectively collected throughout a 3-year period, with special focus upon nonrespiratory features of the disease.. Twenty nusinersen-treated SMA1 patients were included (eight males, median age 13.5 months, interquartile range: 4-56.2 months), among whom 17 survived after 3 years of follow-up. At follow-up, 15 (88%) patients were diagnosed with facial weakness, hypoplasia, or deformity. All but one patient (94%) were fed invasively by percutaneous endoscopic gastrostomy or nasogastric tube feeding. Four patients (25%) had maintained oral feeding in parallel to gastrostomy feeding and had clinical and radiologic evidence of aspirations. Fifteen (88%) patients were diagnosed with scoliosis, of whom seven had undergone or were scheduled to undergo corrective surgery.. Nusinersen-treated SMA1 patients may sustain facial deformities, feeding problems, and severe scoliosis, all of which affect their respiratory system. Strict surveillance of these complications is essential to avoid further respiratory morbidity.

Topics: Humans; Infant; Male; Muscular Atrophy, Spinal; Oligonucleotides; Respiration; Scoliosis; Spinal Muscular Atrophies of Childhood

Topics: Child; Child, Preschool; China; Female; Follow-Up Studies; Humans; Male; Muscular Atrophy, Spinal; Oligonucleotides; Retrospective Studies; Scoliosis; Spinal Muscular Atrophies of Childhood

Intrathecal 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.. Eighteen 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.. Radiation 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.

Topics: Adult; Child; Humans; Injections, Spinal; Muscular Atrophy, Spinal; Oligonucleotides; Radiation Dosage; Retrospective Studies; Scoliosis; Tomography, X-Ray Computed

The approval of nusinersen for the treatment of spinal muscular atrophy (SMA) has significantly changed the natural history of the disease. Nevertheless, scoliosis secondary to axial muscle weakness occurs at some point in most of patients with SMA and a conventional posterior interlaminar approach for intrathecal administration of nusinersen can be particularly challenging to perform in patients with severe scoliosis and/or previous spine fusion surgeries. We developed a protocol for the administration of nusinersen in pediatric patients, which includes a decision-tree algorithm that categorizes patients according to the estimated technical difficulty for the intrathecal administration. Complex spine patients were defined as those with a Cobb angle greater than 50° and/or a history of spinal surgery, while the rest of patients were considered non-complex. Nusinersen was successfully administered through a conventional non-CT-guided lumbar puncture in all 14 non-complex spine patients (110 out of 110 procedures; 100%). The feasibility of the intrathecal injection in the 15 complex spine patients was assessed by 3D CT. Administration was considered unfeasible in 7 out of these 15 patients according to imaging. In the 8 complex spine patients in whom the administration was considered feasible, conventional non-CT-guided lumbar punctures were successful only in 19 out of 53 procedures (36%). The remaining 34 procedures (64%) were guided by CT scan, all successful. Our work demonstrates that a cut-off point of 50° in Cobb angle and history of spinal surgery can reliably be used to anticipate the need for CT guidance in nusinersen administration.

Topics: Adolescent; Algorithms; Child; Child, Preschool; Decision Trees; Feasibility Studies; Female; Humans; Imaging, Three-Dimensional; Infant; Injections, Spinal; Male; Muscular Atrophy, Spinal; Neurosurgical Procedures; Oligonucleotides; Radiography, Interventional; Scoliosis; Tomography, X-Ray Computed

This observational study describes our experience delivering nusinersen through lumbar puncture with real-time ultrasound guidance in spinal muscular atrophy (SMA) patients with severe scoliosis.. Intrathecal nusinersen via real-time ultrasound-guided lumbar puncture was given to three patients who had severe thoracic and lumbar scoliosis: a 34-year-old female with type 3a SMA, a 28-year-old male with type 2a SMA, and a 14-year-old girl with type 3a SMA. Lumbar puncture was performed without sedation under ultrasound guidance using a 22G echogenic needle in the interlaminar aspect of the L4-L5 or L5-S1 interspace and a full dose of nusinersen (12 mg/5 mL) was injected after visualizing free cerebrospinal fluid flow. Patients completed their four loading doses and one maintenance dose of nusinersen. All 15 procedures were successful and well tolerated.. Real-time ultrasound-guided lumbar puncture is an effective and radiation-free technique to administer intrathecal nusinersen in SMA patients with severe scoliosis when done by practitioners with expertise in this procedure.

Topics: Adolescent; Adult; Female; Humans; Male; Muscular Atrophy, Spinal; Oligonucleotides; Scoliosis; Ultrasonography, Interventional

Spinal muscular 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 being one of the most frequent ones. These patients show a high incidence of scoliosis requiring surgery. In 2016 and 2017, the Federal Drug Administration and 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.. We 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 nusi-nersen while reducing the need for sedation and exposure to radiation.

Topics: Adolescent; Catheterization; Catheters, Indwelling; Female; Humans; Injections, Spinal; Laminectomy; Muscular Atrophy, Spinal; Oligonucleotides; Scoliosis; Spinal Fusion; Tomography, X-Ray Computed

Clinical trials data concerning use of nusinersen in older spinal muscular atrophy (SMA) patients is lacking. We describe our center's experience in using intrathecal nusinersen for older patients in the clinical setting.. Retrospective study.. Twelve patients (12-52 years old) were treated with nusinersen. Mean follow-up duration was 17.4 months (range, 4-26 months). All patients had scoliosis; 10 had spinal fusion/instrumentation. All procedures (30 cervical and 57 lumbar punctures) were technically successful. The only side effects were postprocedural headache (9%) and site pain (5.7%). Functional assessments showed stability in 6/9 patients and improvement in 3/9 patients. Subjective improvements in endurance, hand strength, and bulbar functioning critical for activities of daily living were reported in 8/12 patients. None of the patients has discontinued treatment so far.. Intrathecal nusinersen can be safely delivered in older SMA patients. Available functional outcome measures are not adequate to capture meaningful subjective improvements.

Topics: Activities of Daily Living; Adolescent; Adult; Child; Cross-Sectional Studies; Female; Follow-Up Studies; Hand Strength; Humans; Injections, Spinal; Male; Middle Aged; Muscular Atrophy, Spinal; Oligonucleotides; Physical Endurance; Retrospective Studies; Scoliosis; Spinal Fusion; Treatment Outcome; Young Adult

Many children with spinal muscular atrophy (SMA) develop progressive spinal deformity, worsening already compromised pulmonary function and global spinal balance. Early results demonstrate that intrathecal administration of nusinersen, a recent FDA-approved drug, improves motor function and ventilator-free survival, necessitating preservation of intrathecal access when considering PSIF. The purpose of this study is to assess medium-term outcomes of a specialized approach for posterior spinal instrumentation and fusion (PSIF) to preserve intrathecal access in patients with SMA.. A retrospective review of patients with SMA undergoing PSIF at a single tertiary academic medical center during a 3-year period was completed. To facilitate intrathecal drug administration, the traditional approach to PSIF was modified to "skip" one or more intervertebral levels at the thoracolumbar junction. Clinical notes and radiographs were reviewed for postoperative outcomes including major coronal curve correction and complications, including loss of correction, hardware failure and surgical revision.. Eight patients were identified, with a mean age of 12.7 ± 1.6 years and follow-up of 4 years. These patients had a mean preoperative major coronal curve of 56.4°, with mean curve correction of 35.2°. At follow-up, no patients experienced rod breakage, loss of correction, or postoperative chronic pain. Only one patient required revision surgery due to bony overgrowth at the skipped level after three and a half years.. Implementing the skip construct approach for PSIF in patients with SMA allows for scoliosis correction without compromising intrathecal drug delivery. Follow-up at 4 years reveals no adverse clinical events, hardware failure or loss of correction.. IV.

Topics: Adolescent; Disease Progression; Drug Administration Routes; Female; Follow-Up Studies; Humans; Injections, Spinal; Male; Muscular Atrophy, Spinal; Oligonucleotides; Retrospective Studies; Scoliosis; Spinal Fusion; Treatment Outcome

Spinal deformities and surgical correction of scoliosis can make intrathecal delivery of nusinersen very challenging. We aim to evaluate the feasibility and safety of intrathecal administration of nusinersen either via interlaminar or transforaminal approach in a cohort of adult and adolescent patients with spinal muscular atrophy (SMA). Twelve patients were treated with nusinersen in our center under CT-guidance; after a CT scan of the lumbar column, we identified a safe virtual trajectory for the needle and defined patients to address to the transforaminal approach (seven patients) or the interlaminar approach (five patients). Out of 47 procedures, all injections but one were successful. There was one adverse event (post-lumbar puncture syndrome) in the interlaminar approach group (out of 20 procedures) and four adverse events in TFA group (out of 27 procedures) including one serious adverse event, a subarachnoid hemorrhage that required hospitalization. Transforaminal approach can be considered an effective option for nusinersen administration but potentially associated with serious complications, therefore it should be recommended in very selected patients.

Topics: Adolescent; Adult; Female; Humans; Lumbosacral Region; Male; Middle Aged; Muscular Atrophy, Spinal; Oligonucleotides; Scoliosis; Spinal Puncture; Tomography, X-Ray Computed; Young Adult

Nusinsersen is now available in Italy for all SMA types. We describe the experience with intrathecal treatment with nusinersen in 50 patients with SMA at the NEMO Center (NEuroMuscular Omniservice Clinical Center) in Milan, a neuromuscular patient-centered clinic hosted within Niguarda Hospital, a National Public General Hospital. Our results indicate that the pathway of care described outweighs the burden due to the repeated intrathecal injections. Irrespective of age and severity, the treatment is feasible, accessible, and replicable provided that there is a multidisciplinary team having experience and training in SMA.

Topics: Adolescent; Child; Child, Preschool; Delivery of Health Care, Integrated; Family; Geography, Medical; Humans; Infant; Injections, Spinal; Muscular Atrophy, Spinal; Neuroprotective Agents; Oligonucleotides; Patient Care Team; Patient Dropouts; Scoliosis; Spinal Puncture; Spine

This study describes a new procedure for a safer and easier access for the intrathecal injection of the recently approved nusinersen therapy in spinal muscular atrophy. This therapy changed the natural history of the disease, but, to date, scoliosis surgery was an excluding criteria for nusinersen therapy. The bone mass, due to the posterior spinal fusion of the scoliosis surgery, prevents the needle for the nusinersen administration from intervertebral access. This is a single-center, single-surgeon case series descriptive study. A laminotomy at the L3-L4 level was performed to provide safer access for the intrathecal injection. The procedure was carried out during the scoliosis surgery in patients who underwent posterior spinal fusion (PSF) after the nusinersen therapy was introduced, whereas for those who underwent PSF earlier, a second procedure was necessary to perform a laminotomy. A fat grafting was used to prevent bone overgrowth in the laminotomy. Markers were applied as radiographic references for the intrathecal injection. Five patients were enrolled, four females and one male. The mean age of the patients was 11 years. Three patients underwent PSF before the introduction of the nusinersen therapy. Two patients underwent PSF after the nusinersen therapy was available. All of them underwent a laminotomy with a fat grafting at the L3-L4 laminotomy level and received nusinersen therapy without complications. The procedure described is simple and effective in providing safe intrathecal access to make these patients eligible for such important therapy.

Topics: Adolescent; Child; Female; Follow-Up Studies; Humans; Injections, Spinal; Laminectomy; Lumbar Vertebrae; Male; Muscular Atrophy, Spinal; Oligonucleotides; Radiography; Scoliosis; Spinal Fusion