Nusinersen in type 1 SMA infants, children and young adults: Preliminary results on motor function

Pane, Marika; Palermo, Concetta; Messina, Sonia; Sansone, Valeria; Bruno, Claudio; Catteruccia, Michela; Sframeli, Maria; Albamonte, Emilio; Pedemonte, Marina; D’Amico, Adele; Brigati, Giorgia; Sanctis, Roberto De; Coratti, Giorgia; Lucibello, Simona; Bertini, Enrico; Vita, Giuseppe; Tiziano, Francesco Danilo; Mercuri, Eugenio

doi:10.1016/j.nmd.2018.05.010

Cited by 91 publications

(88 citation statements)

References 14 publications

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“…6 This included subdividing them according to the copy number, to the age when they started treatment, and to the severity of the disease. 6 This included subdividing them according to the copy number, to the age when they started treatment, and to the severity of the disease.…”

Section: Discussionmentioning

confidence: 99%

“…Written informed consent was obtained from all participants (or guardians of participants) in the study (consent for research). 6 The assessments were always performed after 12 months from the first dose of nusinersen, between the 6th dose of nusinersen and before the 7th dose, generally performed at 14 months. 11 Measures were performed by clinical evaluators after training and reliability sessions.…”

Section: Methodsmentioning

confidence: 99%

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Nusinersen in type 1 spinal muscular atrophy: Twelve‐month real‐world data

Pane

Coratti

Sansone

et al. 2019

Annals of Neurology

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Objective: The aim of the study was to report 12-month changes after treatment with nusinersen in a cohort of 85 type I spinal muscular atrophy patients of ages ranging from 2 months to 15 years and 11 months. Methods: All patients were assessed using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the Hammersmith Infant Neurological Examination-Section 2 (HINE-2). Results: Two of the 85 patients had 1 SMN2 copy, 61 had 2 copies, and 18 had 3 copies. In 4 patients the SMN2 copy number was not available. At baseline, the mean CHOP INTEND scores ranged between 0 and 52 (mean = 15.66, standard deviation [SD] = AE13.48), and the mean HINE-2 score was between 0 and 5 (mean = 0.69, SD = AE1.23). There was a difference between baseline and the 12-month scores on both the CHOP INTEND and the HINE-2 for the whole group (p < 0.001), the subgroups with 2 SMN2 copies (p < 0.001), and those with 3 SMN2 copies (p < 0.001). The difference was found not only in patients younger than 210 days at baseline (p < 0.001) but also in those younger than 5 years on the CHOP INTEND and younger than 2 years on the HINE-2. Interpretation: Our results, expanding the age range and the severity of type I patients treated with nusinersen over 1 year, provide additional data on the range of efficacy of the drug that will be helpful in making an informed decision on whether to start treatment in patients of different ages and severity.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Nusinersen in type 1 spinal muscular atrophy: Twelve‐month real‐world data

Pane

Coratti

Sansone

et al. 2019

Annals of Neurology

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100

103

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“…SMN2 copy number was not significantly correlated with attainment of the sitting position. Although three copies of SMN2 are not associated with a better prognosis in patients with symptomatic SMA1 treated with nusinersen, preliminary results from a study of infants treated presymptomatically with nusinersen indicated that patients with three SMN2 copies have better improvement than patients with two copies . Neither the median age at first appearance of symptoms nor the age at the start of the treatment was correlated with the achievement of an independent sitting position in our cohort.…”

Section: Discussionmentioning

confidence: 99%

“…Choosing a scale for an objective evaluation of this cohort is challenging. Although the HINE‐2 was developed for infants aged 0 to 24 months, it has become a widely used assessment tool for patients with SMA . In contrast, the CHOP‐INTEND was validated in patients of a broad age range .…”

Section: Discussionmentioning

confidence: 99%

Sitting in patients with spinal muscular atrophy type 1 treated with nusinersen

Aragon-Gawinska

Daron

Ulinici

et al. 2019

Develop Med Child Neuro

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Aim To determine factors associated with acquisition of a sitting position in patients with spinal muscular atrophy type 1 (SMA1) treated with nusinersen. Method Using data from the registry of patients with SMA1 treated with nusinersen, we compared the subgroups of sitters and non‐sitters after 14 months of therapy as a function of baseline level, SMN2 copy number, age at treatment initiation, and improvement at 2 and 6 months post‐treatment initiation. We used Hammersmith Infant Neurological Examination, Section 2 (HINE‐2) and Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders for motor evaluation. Results Fifty children (22 females, 28 males), mean age 22 months (SD 20.7; range 2.5–102.8mo) were treated. Data on sitting position acquisition were collected for 47 patients at month 14. Fifteen patients were able to sit unassisted; 11 of 15 had a baseline HINE‐2 score of at least 2 points and 11 of 14 had an improvement over baseline of at least 2 points at month 6. Patients who improved by 2 or more points at month 6 were three times more likely to be sitters at month 14 than those who did not. Interpretation High baseline motor function and improvement in HINE‐2 score after 6 months of treatment are associated with the probability of acquiring a sitting position in patients with SMA1 treated with nusinersen. What this paper adds Fifteen of 47 patients with spinal muscular atrophy could sit unaided 14 months after treatment with nusinersen. The number of SMN2 copies were not predictive of acquisition of a sitting position. Baseline condition and clinical response after 6 months of treatment were most predictive of sitting position acquisition.

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“…Recently, several reports have outlined preliminary experiences with an alternative technique, transforaminal lumbar puncture (TLFP), especially when used for the administration of intrathecal drugs, for example, nusinersen for treatment of spinal muscular atrophy (SMA) patients (Nascene et al, ; Towbin et al, ; Weaver et al, ). The usual therapeutic course requires that nusinersen be administered intrathecally on multiple occasions (Pane et al, ). However, severe SMA may result in progressive spinal degeneration and scoliosis, often requiring long segment or near complete posterior spinal fusion to manage the scoliosis and forestall further degenerative changes.…”

Section: Introductionmentioning

confidence: 99%

Magnetic resonance imaging anatomy and morphometry of lumbar intervertebral foramina to guide safe transforaminal subarachnoid punctures

2019

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Percutaneous transforaminal lumbar punctures (TFLPs) offer alternative access routes to the lumbar subarachnoid cistern. Safe fluoroscopic insertion of a needle through a lumbar intervertebral foramen (IVF) should ideally avoid the exiting spinal nerve and surrounding vascular pedicles. A crescentic region in the posterior aspect of IVF is the conventional position for needle placement during TFLP, but the underlying anatomic basis for this has not been evaluated fully. To enhance TFLP safety, we defined the morphometry of normal lumbar IVFs and precise locations of neurovascular structures in the IVF posterior crescent. We retrospectively reviewed high‐resolution T2‐weighted lumbar spine magnetic resonance images of 40 normal adults to establish normative dimensions of each IVF from L1 to L5 bilaterally. We segmented the IVF posterior crescent into three parts, and within each, measured the areas occupied by neurovascular structures. We statistically correlated the presence or absence of neurovascular structures in each crescent segment using a chi‐square test. The mean morphometrics for all 304 IVFs in 10 males and 30 females of similar ages were: area 115.3 ± 29.5 mm2; height 18.0 ± 2.4 mm; and width at mid‐disc level 5.6 ± 2.1 mm. We found a significant association between crescent segment and presence or absence of neurovascular structures (χ2 = 95.9, p < .001). A post‐hoc calculation of adjusted standardized residuals identified a significant association between the middle crescent segment and absence of neurovascular structures. Thus, the middle segment of the IVF posterior crescent is significantly most devoid of neurovascular structures, and more often would be the safest target for needle placement during TFLP.

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Nusinersen in type 1 SMA infants, children and young adults: Preliminary results on motor function

Cited by 91 publications

References 14 publications

Nusinersen in type 1 spinal muscular atrophy: Twelve‐month real‐world data

Nusinersen in type 1 spinal muscular atrophy: Twelve‐month real‐world data

Sitting in patients with spinal muscular atrophy type 1 treated with nusinersen

Magnetic resonance imaging anatomy and morphometry of lumbar intervertebral foramina to guide safe transforaminal subarachnoid punctures

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