Neurologic complications of thiamine (B1) deficiency following bariatric surgery in adolescents.

BACKGROUND: The prevalence of obesity among children and adolescents is rising and poses a major health concern. Bariatric surgery is well established in adults and has become an option for adolescents. Thiamine (B1) deficiency is common following bariatric surgery in adults. It may present as Beri-Beri, Wernicke encephalopathy, or Korsakoff psychosis. OBJECTIVE: Our aim was to describe the clinical features, diagnosis, and treatment of adolescents who presented with B1 deficiency after bariatric surgery at one center, and to summarize the data from the literature. PATIENTS: Three adolescents with morbid obesity (two boys and one girl, aged 15.5 to- 17-years-old), presented at Schneider Children's Medical Center of Israel with progressive lower limb pain and weakness 2-3 month following a bariatric procedure (sleeve gastrectomy or narrowing of a bariatric band). The girl also had upper limb involvement and cerebellar signs. All three were non-compliant with micronutrient supplementation. After admission, they received intravenous B1 and oral multivitamin supplementation, and their symptoms improved considerably. CONCLUSIONS: Micronutrient supplementation following bariatric surgery is crucial to prevent deficiencies. In adolescents, compliance with micronutrient supplementation should be assessed before and after such surgery. Thiamine deficiency may cause polyneuropathy, among other symptoms. Treatment reduces the severity of neurological complications.

Evaluation of sputum cultures in children with spinal Muscular atrophy.

BACKGROUND: Spinal Muscular Atrophy (SMA) is a severe neuromuscular disorder. Despite increased survival due to novel therapies, morbidity from respiratory complications still persists. We aim to describe these patients' sputum cultures as an expression of chronic infectious airway disease. METHODS: Retrospective review of medical records of all children with SMA followed at the multidisciplinary respiratory neuromuscular clinic at Schneider Childrens' Medical Center of Israel over a 16-year period. Sputum cultures were obtained during routine visits or pulmonary exacerbations. RESULTS: Sixty-one SMA patients, aged 1 month to 21 years, were included in this cohort. Of these, sputum cultures were collected from 41 patients. Overall, 288 sputum cultures were obtained, and 98 (34%) were negative for bacterial growth. For the first culture taken from each patient, 12 out of 41 (29%) were sterile. The most common bacteria were pseudomonas aeruginosa (PSA) (38%) and staphylococcus aureus (19.6%). PSA was found in SMA type I patients more frequently than in type II patients (15/26 = 58% vs 4/13 = 31%, p < 0.001). PSA infection was positively associated with noninvasive ventilation, recurrent atelectasis, recurrent pneumonias, swallowing difficulties, but no significant association was found with cough assist machine usage. The incidence of positive cultures did not differ between those treated with Onasemnogene abeparvovec or Nusinersen compared to those without treatment, but the age of first PSA isolation was slightly older with Nusinersen treatment (p = 0.01). CONCLUSIONS: Airway bacterial colonization is common in SMA type I patients and is not decreased by Onasemnogene abeparvovec or Nusinersen treatment.

Adeno-associated virus serotype 9 antibody titers in patients with SMA pre-screened for treatment with onasemnogene abeparvovec -routine care evidence.

Spinal muscular atrophy (SMA) is characterized by progressive weakness of skeletal and respiratory muscles. This study aimed to evaluate the prevalence of pre-existing anti adeno-associated virus serotype 9 antibody (AAV9-Ab) titers among infantile-onset SMA diagnosed infants pre-screened for treatment with AAV9-based onasemnogene abeparvovec, and to explore whether clinical and/or demographic characteristics are correlated with AAV9 Ab test results. This is a retrospective multicenter study of children diagnosed with 5q SMA younger than two years of age. The obtained data included demographic data, SMA type, SMN2 gene copy number, onset date, and results of AAV9-Ab test and of SMA prior treatments. Thirty-four patients were enrolled; six patients had positive results of AAV9-Ab (titer > 1:50) in the initial screening, 15 patients were re-tested for AAV9-Abs, of whom, three patients had seroreverted [1.5-4.5 months] between the two AAV9-Abs tests. One patient had seroconverted (5.5 months after the first AAV9-Abs test). The remaining 11 patients presented matching titer results in the two tests. No demographic/clinical factors were correlated to high AAV9-Abs titers (P > 0.05).We recommend AAV9-Ab re-tests to be performed until the age of 8 months, or, if 1.5 months or more have passed after the initial AAV9-Abs test.

The Utility of Early Brain MRI for Patients with Neurofibromatosis Type 1 and Optic Pathway Glioma: A Long-Term Follow-Up in a Tertiary Referral Hospital.

Screening studies have shown detection of optic pathway gliomas (OPGs) in 8 to 31% of children with neurofibromatosis type 1 (NF1). Many of those affected show prolonged indolent phases, but others develop vision disturbances even before diagnosis and treatment. We assessed the clinical presentation at diagnosis, location, natural progression, and risk factors for impaired vision of OPG. The clinical database of the NF1 multidisciplinary clinic of Schneider Children's Medical Center of Israel was reviewed for all patients diagnosed and followed with NF1 during 2007 to 2019. OPG was diagnosed by hyperintensity and thickening along the optic pathway on T2-weighted brain magnetic resonance imaging (MRI), with or without contrast enhancement. Of 257 children with NF1 who underwent MRI, 57 (22%) were diagnosed with OPG; 31 (54%) were females. Twenty-five (44%) had familial NF1. Fifteen (26%) who exhibited tumor progression and worsening in ophthalmic examinations required treatment. Post-chiasmatic glioma was a predictive factor for treatment (p < 0.05), whereas MRI done later and female gender were not significant. Four patients who eventually needed therapy had normal ophthalmic examinations at least 1 year prior to their first MRI. For 6 (40%) of the patients treated, vision continued to worsen. Our findings demonstrate that normal ophthalmic examinations do not always exclude OPG in children with NF1. Early brain MRI before age 36 months may detect OPG, lead to better follow-up and early treatment, and help improve vision outcome.

Impairments in communication and social interaction in children with neurofibromatosis type 1: Characteristics and role of ADHD and language delay.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a multisystem neurocutaneous disorder with increased risk of tumor formation and higher incidence of autism spectrum disorder (ASD) than the general population. The aim of the study was to assess the presence of ASD symptoms in young children with NF1 and to examine their potential association with attention deficit hyperactivity disorder (ADHD) and speech delay. METHODS: The cohort included 30 patients with NF1 attending the multidisciplinary NF1 clinic of a tertiary pediatric medical center from September 2015 through September 2016. The parents/caregivers completed the Social Communication Questionnaire (SCQ) and the Vineland Adaptive Behavior Scales (VABS II). RESULTS: Sixteen patients (53%) had a previous diagnosis of ADHD. There was a positive association between the presence of ADHD and a low score on the VABS II interpersonal relationships subscale of the Socialization domain. Language delay, documented in 12 children (40%), also correlated with a low interpersonal relationships score. CONCLUSIONS: ADHD appears to be more a marker than an actual independent risk factor of ASD in NF1. The early evaluation of children with NF1 for interpersonal communication problems and ASD, especially those with a speech delay or ADHD, will alert clinicians to initiate appropriate and timely treatment.

Impact of a national population-based carrier-screening program on spinal muscular atrophy births.

Spinal muscular atrophy (SMA) is a genetic neurodegenerative disease. Population carrier screening for SMA was introduced in Israel in 2008 through health-care services' insurance plans and expanded to the entire Israeli population in 2013 by a national health program. The aim of the study was to evaluate the impact of carrier screening on reducing the rate of birth of infants with SMA. All cases of prenatal and postnatal diagnosis of SMA in 2008-2017 were identified from databases of relevant government organizations, genetic laboratories in medical centers, and health care systems in Israel. Since 2013, screening was performed in 309,352 individuals, of whom 5741 were found to be carriers (carrier rate 1:54). Given an average of 180,000 live births annually, the predicted rate of SMA diagnosis was 15 cases per year. Prior to 2013, the average rate of prenatally diagnosed SMA was 4.66 cases per year, compared with 7.75 cases per year following population-wide provision of screening. The annual rate of postnatally diagnosed cases remained steady since 2008, with an average of 7- 7.25 cases per year. Screening has been effective in increasing prenatal detection of SMA but has had no effect on the rate of confirmed postnatal diagnoses. We speculate that screening rates may be affected by social, cultural, and religious factors.

Prognostic Parameters of Acute Transverse Myelitis in Children.

Acute transverse myelitis is a rare and disabling disorder. Data on the imaging features in children are sparse. The aim of this study was to describe the clinical and magnetic resonance imaging findings characteristic of pediatric idiopathic acute transverse myelitis and to identify those with prognostic value. The database of a tertiary pediatric medical center was retrospectively reviewed for patients aged less than 18 years who were diagnosed in 2002-2017 with acute transverse myelitis that was not associated with recurrence of a demyelinating autoimmune event. Data were collected on clinical, laboratory, and imaging findings and outcome. A total of 23 children (11 male, 12 female) met the study criteria. Mean age at disease onset was 10 years, and mean duration of follow-up was 6 years 10 months. Spinal cord and brain magnetic resonance imaging scans were performed on admission or shortly thereafter. The most common finding was cross-sectional involvement, in 16 patients (70%). The mean number of involved spinal segments was 8. The most frequently involved region was the thoracic spine, in 17 patients (74%). Clinical factors predicting good prognosis were cerebrospinal fluid pleocytosis, absence of tetraparesis, and prolonged time to nadir. In conclusion, most children with acute transverse myelitis appear to have a good outcome. Prompt diagnosis and treatment are important. Further research is needed in a larger sample to evaluate the predictive value of imaging features.

Small-fiber neuropathy associated with autoinflammatory syndromes in children and adolescents.

INTRODUCTION: Small-fiber neuropathy is rare in children. It has been associated with several autoimmune disorders, but there are no reports of an autoinflammatory etiology. METHODS: The data of four children/adolescents presenting with erythromelalgia and neuropathic pain from 2014 to 2019 were collected retrospectively from the electronic database of a pediatric medical center. RESULTS: Results of clinical and/or electrophysiological evaluation excluded large nerve fiber involvement. Skin biopsy results confirmed small-fiber neuropathy. According to genetic analysis, two patients were heterozygous and one was homozygous for mutations in the familial Mediterranean fever (MEFV) gene. Behcet disease was diagnosed in the fourth patient. Treatment with anti-interleukin-1 agents, intravenous immunoglobulin, and glucocorticoids was beneficial. DISCUSSION: The diagnosis of small-fiber neuropathy should be considered in children/adolescents presenting with erythromelalgia. A thorough investigation is required to reveal the underlying disorder. Clinicians should be alert to the peripheral neurological manifestations of autoinflammatory syndromes because effective treatments are available.

Thick Corpus Callosum in Children.

BACKGROUND AND PURPOSE: A thick corpus callosum (TCC) can be associated with a very grave outcome in fetuses, but its clinical presentation in older children seems to be markedly different. METHODS: The corpus callosum (CC) was defined as thick based on observations and impressions. We reviewed cases of children who were diagnosed as TCC based on brain magnetic resonance imaging (MRI) studies. The pertinent clinical data of these children were collected, and their CCs were measured. RESULTS: Out of 2,552 brain MRI images, those of 37 children were initially considered as showing a TCC. Those initial imaging were reviewed by an experienced neuroradiologist, who confirmed the diagnosis in 34 children (1.3%): 13 had neurofibromatosis-1 (NF-1), 9 had epilepsy, 3 had macrocephaly capillary malformation (MCM) syndrome, 3 had autistic spectrum disorder, 1 had a Chiari-1 malformation, and 1 had increased head circumference. No specific neurologic disorder could be defined in seven children. The measured thickness of the CC in these children was comparable to those published in the literature for adults. CONCLUSIONS: A TCC is a rare brain malformation that can be found in neuropathologies with apparently diverse pathognomonic mechanisms, such as NF-1 and MCM. It is not necessarily associated with life-threatening conditions, instead being a relatively benign finding, different in nature from that reported in fetuses.

Brain imaging findings and social/emotional problems in Israeli children with neurofibromatosis type 1.

UNLABELLED: A potential association between brain MRI findings and social/emotional difficulties in children with neurofibromatosis type 1 (NF1) was examined. Twenty-eight children with NF1 filled in the Strengths and Difficulties Questionnaire (SDQ), and possible associations between their responses and findings in their brain MRI were sought. T2 bright foci were identified in MRI scans of 24 patients (85 %). There were no associations between the presence of the bright foci in any specific brain region and any of the SDQ scores for the emotional/behavioral measures. Male patients had significantly abnormal SDQ scores and peer problems. Patients with abnormal SDQ scores were younger than those with normal SDQ scores (mean 13.2 years vs 14.3 years, respectively; p = 0.23). A comparison of the scores obtained in ours and in another group of 11 children with NF1 yielded a significant difference between the groups. CONCLUSION: We believe that the lack of correlation between the MRI findings and the social/emotional parameters of the SDQ is another demonstration of the marked clinical variability characteristic of NF1.

Variable myopathic presentation in a single family with novel skeletal RYR1 mutation.

We describe an autosomal recessive heterogeneous congenital myopathy in a large consanguineous family. The disease is characterized by variable severity, progressive course in 3 of 4 patients, myopathic face without ophthalmoplegia and proximal muscle weakness. Absence of cores was noted in all patients. Genome wide linkage analysis revealed a single locus on chromosome 19q13 with Zmax = 3.86 at θ = 0.0 and homozygosity of the polymorphic markers at this locus in patients. Direct sequencing of the main candidate gene within the candidate region, RYR1, was performed. A novel homozygous A to G nucleotide substitution (p.Y3016C) within exon 60 of the RYR1 gene was found in patients. ARMS PCR was used to screen for the mutation in all available family members and in an additional 150 healthy individuals. This procedure confirmed sequence analysis and did not reveal the A to G mutation (p.Y3016C) in 300 chromosomes from healthy individuals. Functional analysis on EBV immortalized cell lines showed no effect of the mutation on RyR1 pharmacological activation or the content of intracellular Ca(2+) stores. Western blot analysis demonstrated a significant reduction of the RyR1 protein in the patient's muscle concomitant with a reduction of the DHPRα1.1 protein. This novel mutation resulting in RyR1 protein decrease causes heterogeneous clinical presentation, including slow progression course and absence of centrally localized cores on muscle biopsy. We suggest that RYR1 related myopathy should be considered in a wide variety of clinical and pathological presentation in childhood myopathies.