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Objective: To study vamorolone, a first-in-class steroidal anti-inflammatory drug, in Duchenne muscular dystrophy (DMD)., Methods: An open-label, multiple-ascending-dose study of vamorolone was conducted in 48 boys with DMD (age 4-<7 years, steroid-naive). Dose levels were 0.25, 0.75, 2.0, and 6.0 mg/kg/d in an oral suspension formulation (12 boys per dose level; one-third to 10 times the glucocorticoid dose in DMD). The primary goal was to define optimal doses of vamorolone. The primary outcome for clinical efficacy was time to stand from supine velocity., Results: Oral administration of vamorolone at all doses tested was safe and well tolerated over the 24-week treatment period. The 2.0-mg/kg/d dose group met the primary efficacy outcome of improved muscle function (time to stand; 24 weeks of vamorolone treatment vs natural history controls), without evidence of most adverse effects of glucocorticoids. A biomarker of bone formation, osteocalcin, increased in vamorolone-treated boys, suggesting possible loss of bone morbidities seen with glucocorticoids. Biomarker outcomes for adrenal suppression and insulin resistance were also lower in vamorolone-treated patients with DMD relative to published studies of glucocorticoid therapy., Conclusions: Daily vamorolone treatment suggested efficacy at doses of 2.0 and 6.0 mg/kg/d in an exploratory 24-week open-label study., Classification of Evidence: This study provides Class IV evidence that for boys with DMD, vamorolone demonstrated possible efficacy compared to a natural history cohort of glucocorticoid-naive patients and appeared to be tolerated., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: This study explores a large panel of cytokines in plasma and CSF of patients with Aicardi-Goutières syndrome (AGS) at different ages, in order to establish signatures of cytokines most predictive of AGS., Methods: Plasma from 22 subjects with known mutations were assayed for cytokines using the Milliplex MAP Immunobead system, and compared to results from 8 age-matched normal controls. CSF of 11 additional patients with mutation-proven AGS was tested in an identical manner and compared to results from age-matched controls. Samples were banked and analysis was carried out retrospectively., Results: Significant elevations were seen in FMS-related tyrosine kinase 3 ligand, IP-10, interleukin (IL)-12p40, IL-15, tumor necrosis factor α, and soluble IL 2 receptor α in both AGS patient plasma and CSF relative to controls. Additionally, this cytokine signature was able to correctly cluster 9 of 11 AGS cases based on CSF values. While most cytokines decreased exponentially with age, a subgroup including IP-10 demonstrated persistent elevation beyond early childhood., Conclusion: Patients with AGS exhibit plasma and CSF elevations of proinflammatory cytokines. Selected cytokines remain persistently elevated beyond the initial disease phase. This panel of proinflammatory cytokines may be considered for use as diagnostic and therapeutic markers of disease, and may permit improved understanding of disease pathogenesis.

We report the results of 18 recurrent clubfeet in 13 children after Kite's method of casting treated successfully by Ponseti's technique. The average age was 8.3 months. The average preoperative Pirani's midfoot contracture score was 1.8, hindfoot contracture score was 2.4, and total score was 4.2. All patients had full correction of deformities with plantigrade feet and the scores were reduced to zero at the end of treatment. Three recurrences were found at 6 months follow-up, amounting to 17% failure rate. Two of them necessitated percutaneous tenotomy of the tendoachilles, and one underwent posteromedial soft tissue release with good result at the end of 1 year. Ponseti's method is an effective treatment option in the management of recurrent clubfeet after Kite's method. Although short-term results are promising, larger series with long-term follow-up is warranted.

We report a case of congenital pseudarthrosis of the ulna along with generalized neurofibromatosis (type I). The patient had a good clinical outcome after single-bone forearm reconstruction. In the setting of radial head dislocation following long-standing congenital pseudarthrosis of the ulna, single-bone forearm reconstruction is a viable option. It prevents the loss of hand function by the effective shortening of flexor tendons and spares movements of the humeroulnar and radiocarpal joints.