Publications by authors named "Saunder M Bernes"

4 Publications

  • Page 1 of 1

A comprehensive institutional overview of intrathecal nusinersen injections for spinal muscular atrophy.

Pediatr Radiol 2018 11 18;48(12):1797-1805. Epub 2018 Jul 18.

Department of Radiology, Phoenix Children's Hospital, 1919 E. Thomas Road, Phoenix, AZ, 85016, USA.

Background: Spinal muscular atrophy (SMA) is an autosomal-recessive neuromuscular disorder resulting in progressive muscle weakness. In December 2016, the U.S. Food and Drug Administration approved the first treatment for SMA, a drug named nusinersen (Spinraza) that is administered intrathecally. However many children with SMA have neuromuscular scoliosis or spinal instrumentation resulting in challenging intrathecal access. Therefore alternative routes must be considered in these complex patients.

Objective: To investigate routes of drug access, we reviewed our institutional experience of administering intrathecal nusinersen in all children with spinal muscular atrophy regardless of spinal anatomy or instrumentation.

Materials And Methods: We reviewed children with SMA who were referred for intrathecal nusinersen injections from March to December 2017 at our institution. In select children with spinal hardware, spinal imaging was requested to facilitate pre-procedure planning. Standard equipment for intrathecal injections was utilized. All children were followed up by their referring neurologist.

Results: A total of 104 intrathecal nusinersen injections were performed in 26 children with 100% technical success. Sixty procedures were performed without pre-procedural imaging and via standard interspinous technique. The remaining 44 procedures were performed in 11 complex (i.e. neuromuscular scoliosis or spinal instrumentation) patients requiring pre-procedural imaging for planning purposes. Nineteen of the 44 complex procedures were performed via standard interspinous technique from L2 to S1. Twenty-two of the 44 complex procedures were performed using a neural-foraminal approach from L3 to L5. Three of the 44 complex procedures were performed via cervical puncture technique. There were no immediate or long-term complications but there was one child with short-term complications of meningismus and back pain at the injection site.

Conclusion: Although we achieved 100% technical success in intrathecal nusinersen administration, our practices evolved during the course of this study. As a result of our early experience we developed an algorithm to assist in promoting safe and effective nusinersen administration in children with spinal muscular atrophy regardless of SMA type, abnormal spinal anatomy and complex spinal instrumentation.
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November 2018

Outcomes of thoracoscopic thymectomy in patients with juvenile myasthenia gravis.

J Pediatr Surg 2016 Jul 6;51(7):1078-83. Epub 2016 Jan 6.

Department of Surgery, Mayo Clinic, Phoenix, AZ; Department of Surgery, Phoenix Children's Hospital, Phoenix, AZ. Electronic address:

Introduction: Myasthenia gravis (MG) is an autoimmune disorder of the postsynaptic neuromuscular junction resulting in fatigability of voluntary muscles. There has been increasing evidence supporting thymectomy for MG in adults, and evidence for the role of surgery in pediatric age groups is increasing. The purpose of this study is to describe the outcomes of our patients with juvenile MG undergoing thoracoscopic thymectomy.

Material And Methods: All patients with juvenile MG who underwent thoracoscopic thymectomy at Phoenix Children's Hospital between 1999 and 2014 were included. Patients were diagnosed by their treating neurologist. An Osserman and Genkins criterion was used to classify the severity of the disease and DeFilippi classification was used to assess remission.

Results: Twelve patients underwent thoracoscopic thymectomy for juvenile MG during the time frame studied. Nine (75%) patients had an Osserman stage of IIB, with only two patients with ocular disease. There were no conversions to an open procedure. Seven (59%) patients had normal thymic histology, 4 (33%) had evidence of follicular hyperplasia and one (8%) had involutional changes. The median length of hospital stay was 2days (range 1-5days). There was no 30-day postoperative morbidity, reoperations or mortality. The median length of follow-up was 31months (range, 4-91months) and at the time of their last follow-up; all 12 (100%) patients had a DeFilippi Classification of 3 or better.

Conclusion: Surgery for MG in children is indicated for antibody-receptor-positive patients with moderate to severe disease. Thoracoscopic thymectomy is a safe and acceptable treatment for juvenile MG with good disease control. The low morbidity and shorter hospital duration make it an excellent option for consideration.
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July 2016

Novel pathogenic variants and genes for myopathies identified by whole exome sequencing.

Mol Genet Genomic Med 2015 Jul 8;3(4):283-301. Epub 2015 Apr 8.

Integrated Cancer Genomics, Translational Genomics Research Institute (TGen) Phoenix, Arizona.

Neuromuscular diseases (NMD) account for a significant proportion of infant and childhood mortality and devastating chronic disease. Determining the specific diagnosis of NMD is challenging due to thousands of unique or rare genetic variants that result in overlapping phenotypes. We present four unique childhood myopathy cases characterized by relatively mild muscle weakness, slowly progressing course, mildly elevated creatine phosphokinase (CPK), and contractures. We also present two additional cases characterized by severe prenatal/neonatal myopathy. Prior extensive genetic testing and histology of these cases did not reveal the genetic etiology of disease. Here, we applied whole exome sequencing (WES) and bioinformatics to identify likely causal pathogenic variants in each pedigree. In two cases, we identified novel pathogenic variants in COL6A3. In a third case, we identified novel likely pathogenic variants in COL6A6 and COL6A3. We identified a novel splice variant in EMD in a fourth case. Finally, we classify two cases as calcium channelopathies with identification of novel pathogenic variants in RYR1 and CACNA1S. These are the first cases of myopathies reported to be caused by variants in COL6A6 and CACNA1S. Our results demonstrate the utility and genetic diagnostic value of WES in the broad class of NMD phenotypes.
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July 2015

Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities.

Nat Genet 2008 Dec;40(12):1466-71

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.

Chromosome region 1q21.1 contains extensive and complex low-copy repeats, and copy number variants (CNVs) in this region have recently been reported in association with congenital heart defects, developmental delay, schizophrenia and related psychoses. We describe 21 probands with the 1q21.1 microdeletion and 15 probands with the 1q21.1 microduplication. These CNVs were inherited in most of the cases in which parental studies were available. Consistent and statistically significant features of microcephaly and macrocephaly were found in individuals with microdeletion and microduplication, respectively. Notably, a paralog of the HYDIN gene located on 16q22.2 and implicated in autosomal recessive hydrocephalus was inserted into the 1q21.1 region during the evolution of Homo sapiens; we found this locus to be deleted or duplicated in the individuals we studied, making it a probable candidate for the head size abnormalities observed. We propose that recurrent reciprocal microdeletions and microduplications within 1q21.1 represent previously unknown genomic disorders characterized by abnormal head size along with a spectrum of developmental delay, neuropsychiatric abnormalities, dysmorphic features and congenital anomalies. These phenotypes are subject to incomplete penetrance and variable expressivity.
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December 2008