Ultrasound-assisted or Landmark-based Intrathecal Administration of Nusinersen in Adult Patients With Spinal Muscular Atrophy (The EchoSpin Study) (EchoSpin)

Interlaminar Ultrasound-assisted or Landmark-based Intrathecal Administration of Nusinersen in Adult Patients With Spinal Muscular Atrophy: a Retrospective Analysis of More Than 500 Consecutive Administrations

Nusinersen (Spinraza, Biogen Inc, Boston, MA), the first treatment approved by FDA and EMA for all Spinal Muscular Atrophy (SMA) subtypes, is an antisense oligonucleotide that is administered intrathecally through a lumbar puncture. This procedure can be challenging in some adults with intermediate and late onset SMA (types II-IV) frequently presenting scoliosis secondary to neuromuscular weakness and often treated with spinal instrumentation to prevent worsening deformities.

In such patients, in order to access the intrathecal space, US guidance and/or assistance have been recently proposed as useful and successful tool. The US guidance and/or assistance have been associated to a high success rate, a reduction of number of attempts and needle passes to obtain a successful anesthesia. A reduced risk of adverse events (AEs), such as post dural puncture headache (PDPH) and low back pain (LBP), and low patient satisfaction often associated with multiple needle punctures was also reported.

Aim of this retrospective study was to report the efficacy, evaluated as rate of the successful procedures and subsequent delivery of nusinersen within the subarachnoid space, the number of attempts, the procedure time and the adverse events (AEs) of interlaminar intrathecal nusinersen administration using either ultrasound assistance or the landmark-based technique in a historical cohort of 51 adult SMA patients.

Study Overview

• Status: Completed
• Conditions: Ultrasonography; Spinal Muscular Atrophy; Anesthesia, Spinal; Spinal Puncture Complications
• Intervention / Treatment: Procedure: Interlaminar ultrasound-assisted intrathecal administration of nusinersen; Procedure: Landmark-based intrathecal administration of nusinersen

• Study Type: Observational
• Enrollment (Actual): 51

Contacts and Locations

Study Locations

• Italy
  • RM
    • Roma, RM, Italy
      • Fondazione Policlinico Gemelli

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

51 adults with a genetically confirmed diagnosis of SMA (13 SMA type 2, 38 SMA type 3) consecutively treated with nusinersen intrathecal administration between April 2018 and August 2022 in "Policlinico A. Gemelli" in Rome.

Description

Inclusion Criteria:

• A genetically confirmed diagnosis of SMA
• Treatment with nusinersen

Exclusion Criteria:

• congenital coagulopathy,
• localized infections,
• increased intracranial pressure.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

SMA patients; 51 adults with a genetically confirmed diagnosis of SMA (13 SMA type 2, 38 SMA type 3) treated with nusinersen. The technique used was based on the anesthesiologist's preference.

Procedure: Interlaminar ultrasound-assisted intrathecal administration of nusinersen; All procedures were performed with patients either seated or placed in a lateral decubitus. After skin disinfection with 2% chlorhexidine in 70% alcohol, using a convex array, the L3-4 or L4-5 intervertebral space was identified and a left paramedian sagittal oblique view was obtained; the probe was rotated 90° into a transverse orientation, centered on the neuraxial midline, and moved in either the cephalad or caudal direction to obtain a transverse interlaminar view; the intersection between the two markings of the spinal midline and interspinous space was identified as the spinal entry point of the needle. After local anesthesia (LA) with lidocaine 2%, a 25-gauge non-traumatic 90 mm Whitacre spinal needle or a traumatic 90 mm Quincke spinal needle was used to access the subarachnoid space. After confirmation of cerebrospinal fluid (CSF) flow, 5 mL of CSF were removed. Subsequently, nusinersen was administered intrathecally over 1-3 min.; Procedure: Landmark-based intrathecal administration of nusinersen; All procedures were performed with patients placed in their most comfortable position (either seated or placed in a lateral decubitus). After skin disinfection with 2% chlorhexidine in 70% alcohol, conventional palpation of the superior aspect of iliac crest was performed and the palpated intercristal line was assumed to cross the spine at L4 vertebral body or L4-L5 interspace. The skin was marked with horizontal and vertical lines at the L3-L4 or L2-L3 interspaces and was referred as entry point of the needle. The procedure was then completed in the same fashion as for US-assisted technique.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of successful administrations	Defined as a confirmation of the CSF flow through the spinal needle and subsequent administration of whole drug	During the procedure
Number of attempts	Defined as the number of needle insertions through the skin surface	During the procedure
Procedure time	The time in minutes from the start of US imaging or the palpation of superior aspect of iliac crest to visualization of CSF flow	During the procedure
Number of technical success procedures	Defined as a successful intrathecal administration with equal or less than 4 attempts	During the procedure
Adverse events (AEs)	Defined as mild AEs (Post Dural Puncture Headache, Low Back Pain) or severe AEs (spinal cord injury/epidural hematoma, abdominal organ lesions)	In the first 72 hours after the procedure

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: Bruno A Zanfini, Fondazione Policlinico A. Gemelli

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2022
• Primary Completion (Actual): January 10, 2023
• Study Completion (Actual): January 10, 2023

Study Registration Dates

• First Submitted: November 30, 2022
• First Submitted That Met QC Criteria: November 30, 2022
• First Posted (Actual): December 9, 2022

Study Record Updates

• Last Update Posted (Estimate): March 9, 2023
• Last Update Submitted That Met QC Criteria: March 7, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Spinal Cord Diseases; Motor Neuron Disease; Muscular Atrophy; Atrophy; Muscular Atrophy, Spinal
• Other Study ID Numbers: EchoSpin

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No