Citation: carson vj, young m, brigatti kw, et al.Nusinersen by subcutaneous intrathecal catheter for symptomatic spinal muscular atrophy patients with complex spine anatomy.Muscle nerve.2021.10.1002/mus.27425 summary/abstract: introduction/aims: intrathecal administration of nusinersen is challenging in patients with spinal muscular atrophy (sma) who have spine deformities or fusions.We prospectively studied the safety and efficacy of nusinersen administration via an indwelling subcutaneous intrathecal catheter (sic) for sma patients with advanced disease.Methods: seventeen participants commenced nusinersen therapy between 2.7 and 31.5 years of age and received 9-12 doses via sic.Safety was assessed in all participants.A separate efficacy analysis comprised 11 non-ambulatory, treatment-naïve sma patients (18.1±6.8 years) with three smn2 copies and complex spine anatomy.Results: in the safety analysis, 14 treatment-related adverse events (aes) occurred among 12 (71%) participants; all were related to the sic and not nusinersen.Device-related aes interfered with 2.5% of nusinersen doses.Four sics (24%) required surgical revision due to mechanical malfunction with or without cerebrospinal fluid leak (n=2), and one (6%) was removed due to (b)(6) meningitis.In the efficacy analysis, mean performance on the nine hole peg test improved in dominant (15.9%, p=0.0.012) and non-dominant (19.0%, p=0.008) hands and grip strength increased 44.9% (p=0.0.031).We observed no significant changes in motor scales, muscle force, pulmonary function, or sma biomarkers.All participants in the efficacy cohort reported one or more subjective improvements of endurance, purposeful hand use, arm strength, head control, and/or speech.Discussion: for sma patients with complex spine anatomy, the sic allows for reliable outpatient administration of nusinersen that results in meaningful improvements of upper limb function, but introduces risks of technical malfunction and iatrogenic infection.Reported events: we recorded 26 adverse events (aes) among 12 study participants who received an aggregate of 203 nusinersen doses (table 2).All 14 treatment-related aes were attributable to the sic device and not nusinersen.Device complications such as wound dehiscence (n=1), mechanical malfunction (n=5), and csf leak (n=2) prompted five outpatient surgical revisions among four participants.Mechanical malfunctions interfered with 2.5% of outpatient nusinersen doses; these included four occlusions of the intrathecal catheter and one fracture of the catheter at its interface with the injection port.One participant presented with headache and low grade fever after the twelfth nusinersen dose and grew (b)(6) from the csf reservoir, prompting its permanent removal.We analyzed 138 csf samples withdrawn from the sic (average eight per participant).The most common treatment-related abnormality was elevated csf red blood cells (rbc) in half of all samples (table s1).The rbc count exceeded 10 per ul in 23% of csf samples and the highest recorded value was 8,520 rbcs/ul.All participants with elevated csf rbcs were asymptomatic.
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Citation: carson vj, young m, brigatti kw, et al.Nusinersen by subcutaneous intrathecal catheter for symptomatic spinal muscular atrophy patients with complex spine anatomy.Muscle nerve.2021.10.1002/mus.27425.This value is the average age of the patients reported in the article as specific patients could not be identified.This value reflects the gender of the majority of the patients reported in the article as specific patients could not be identified.Date of event: please note that this date is based off of the start date of the study as the event dates were not provided in the published literature.If information is provided in the future, a supplemental report will be issued.
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