Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy
NEW ENGLAND JOURNAL OF MEDICINE
2018; 378 (7): 625?35
Management of a Ventral Cerebrospinal Fluid Leak With a Lumbar Transforaminal Epidural Blood Patch in a Child With Persistent Postdural Puncture Headache: A Case Report.
Regional anesthesia and pain medicine
2017; 42 (2): 263-266
Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 ( SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA).We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2:1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was the least-squares mean change from baseline in the Hammersmith Functional Motor Scale-Expanded (HFMSE) score at 15 months of treatment; HFMSE scores range from 0 to 66, with higher scores indicating better motor function. Secondary end points included the percentage of children with a clinically meaningful increase from baseline in the HFMSE score (?3 points), an outcome that indicates improvement in at least two motor skills.In the prespecified interim analysis, there was a least-squares mean increase from baseline to month 15 in the HFMSE score in the nusinersen group (by 4.0 points) and a least-squares mean decrease in the control group (by -1.9 points), with a significant between-group difference favoring nusinersen (least-squares mean difference in change, 5.9 points; 95% confidence interval, 3.7 to 8.1; P<0.001). This result prompted early termination of the trial. Results of the final analysis were consistent with results of the interim analysis. In the final analysis, 57% of the children in the nusinersen group as compared with 26% in the control group had an increase from baseline to month 15 in the HFMSE score of at least 3 points (P<0.001), and the overall incidence of adverse events was similar in the nusinersen group and the control group (93% and 100%, respectively).Among children with later-onset SMA, those who received nusinersen had significant and clinically meaningful improvement in motor function as compared with those in the control group. (Funded by Biogen and Ionis Pharmaceuticals; CHERISH ClinicalTrials.gov number, NCT02292537 .).
View details for DOI 10.1056/NEJMoa1710504
View details for Web of Science ID 000425000000008
View details for PubMedID 29443664
Postdural puncture headache (PDPH) is an uncommon sequel of lumbar puncture in children. When conservative treatment with bed rest, hydration, and caffeine are ineffective, epidural blood patches are recommended and are generally effective. The purpose of this report was to highlight that when lumbar epidural blood patches fail to eliminate PDPH, diagnostic evaluation should be performed and alternative treatment sought.An unusual case is described of an 11-year-old boy with PDPH, which was successfully managed with a ventral (anterior) epidural blood patch and epidural saline infusion after headache and other symptoms failed to resolve after conservative treatment and conventionally performed blood patches.Ineffectiveness of conservative measures and epidural blood patches performed posteriorly to resolve PDPH should lead the physician both to question the diagnosis of PDPH by pursuing radiographic confirmation of a cerebral spinal fluid leak and, furthermore, identification of its location to best direct further therapy.
View details for DOI 10.1097/AAP.0000000000000562
View details for PubMedID 28178090