Vulnerable Child Syndrome and Newborn Screening Carrier Results for Cystic Fibrosis or Sickle Cell.

J Pediatr. 2020 Sep;224:44-50.e1

Authors: Farrell MH, Sims AM, La Pean Kirschner A, Farrell PM, Tarini BA

Abstract
OBJECTIVES: To measure parental perceptions of child vulnerability, as a precursor to developing a population-scale mechanism to mitigate harm after newborn screening.
STUDY DESIGN: Participants were parents of infants aged 2-5 months. Parental perceptions of child vulnerability were assessed with an adapted version of the Vulnerable Baby Scale. The scale was included in the script for a larger study of telephone follow-up for 2 newborn blood screening samples (carrier status for cystic fibrosis or sickle cell hemoglobinopathy). A comparison sample was added using a paper survey with well-baby visits to an urban/suburban clinic.
RESULTS: Sample sizes consisted of 288 parents in the cystic fibrosis group, 426 in the sickle cell hemoglobinopathy group, and 79 in the clinic comparison group. Parental perceptions of child vulnerability were higher in the sickle cell group than cystic fibrosis group (P < .0001), and both were higher than the clinic comparison group (P < .0001). Parental perceptions of child vulnerability were inversely correlated with parental age (P < .002) and lower health literacy (P < .015, sickle cell hemoglobinopathy group only).
CONCLUSIONS: Increased parental perceptions of child vulnerability seem to be a bona fide complication of incidental newborn blood screening findings, and healthcare professionals should be alert to the possibility. From a public health perspective, we recommend routine follow-up after incidental findings to mitigate psychosocial harm.

PMID: 32826027 [PubMed - as supplied by publisher]

CFTR Modulators: Impact on Fertility, Pregnancy, and Lactation in Women with Cystic Fibrosis.

J Clin Med. 2020 Aug 21;9(9):

Authors: Taylor-Cousar JL

Abstract
Cystic fibrosis (CF) is a life-shortening genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. These mutations lead to abnormal ion transport in mucous membranes throughout the body, including in the respiratory and gastrointestinal and reproductive tracts. Improvements in care and therapy have led to substantial increases in the quantity and quality of life for those with CF. Consequently, women with CF are increasingly interested in having families. Although pregnancy was once discouraged for women with CF, at this point, even women with moderately severe lung disease can successfully navigate pregnancy. With the recent approval of a triple combination CFTR modulator therapy that improves lung function, nutritional status, and quality of life for people with a single copy of the most common CFTR mutation, it is expected that the number of women with CF who choose to become pregnant will continue to increase. Although animal reproduction models show no alarming signals for use during pregnancy at normal human doses, there is a paucity of human safety data in pregnancy and lactation. This review summarizes what is currently known about the impact of use of CFTR modulators on fertility, pregnancy, and lactation in women with CF.

PMID: 32825766 [PubMed - as supplied by publisher]

From Ivacaftor to Triple Combination: A Systematic Review of Efficacy and Safety of CFTR Modulators in People with Cystic Fibrosis.

Int J Mol Sci. 2020 Aug 16;21(16):

Authors: Gramegna A, Contarini M, Aliberti S, Casciaro R, Blasi F, Castellani C

Abstract
Over the last years CFTR (cystic fibrosis transmembrane conductance regulator) modulators have shown the ability to improve relevant clinical outcomes in patients with cystic fibrosis (CF). This review aims at a systematic research of the current evidence on efficacy and tolerability of CFTR modulators for different genetic subsets of patients with CF. Two investigators independently performed the search on PubMed and included phase 2 and 3 clinical trials published in the study period 1 January 2005-31 January 2020. A final pool of 23 papers was included in the systematic review for a total of 4219 patients. For each paper data of interest were extracted and reported in table. In terms of lung function, patients who had the most beneficial effects from CFTR modulation were those patients with one gating mutation receiving IVA (ivacaftor) and patients with p.Phe508del mutation, both homozygous and heterozygous, receiving ELX/TEZ/IVA (elexacaftor/tezacaftor/ivacaftor) had the most relevant beneficial effects in term of lung function, pulmonary exacerbation decrease, and symptom improvement. CFTR modulators showed an overall favorable safety profile. Next steps should aim to systematize our comprehension of scientific data of efficacy and safety coming from real life observational studies.

PMID: 32824306 [PubMed - as supplied by publisher]

Selectively targeting key inflammatory pathways in cystic fibrosis.

Eur J Med Chem. 2020 Aug 09;206:112717

Authors: Costantini C, Puccetti M, Pariano M, Renga G, Stincardini C, D'Onofrio F, Bellet MM, Cellini B, Giovagnoli S, Romani L

Abstract
Cystic fibrosis (CF) is a rare genetic disorder caused by a defect in the ion channel Cystic Fibrosis Transmembrane conductance Regulator (CFTR), resulting in ionic imbalance of surface fluid. Although affecting multiple organs, the progressive deterioration of respiratory function by recurrent infections and chronic inflammation represents the main cause of morbidity and mortality in CF patients. The development of modulators targeting the basic defect of CFTR has represented a major breakthrough in CF therapy, but the impact on inflammation has remained enigmatic. The emerging scenario taking hold in the field points to inflammation as a major, somehow missed, therapeutic target for prevention of lung decline. Not surprisingly, the development of anti-inflammatory drugs is taking its share in the drug development pipeline. But the path is not straightforward and targeting inflammation should be balanced with the increased risk of infection. The strategy to restore the homeostatic regulation of inflammation to efficiently respond to infection while preventing lung damage needs to be based on identifying and targeting endogenous immunoregulatory pathways that are defective in CF. We herein provide an overview of anti-inflammatory drugs currently approved or under investigation in CF patients, and present our recent studies on how the knowledge on defective immune pathways in CF may translate into innovative and selective anti-inflammatory therapeutics. Through the discovery of naturally occurring molecules or their synthetic mimics, this review emphasizes the critical importance of selectively targeting key inflammatory pathways to preserve immunocompetence in CF patients.

PMID: 32823008 [PubMed - as supplied by publisher]

Cystic Fibrosis Related Diabetes - An Update.

QJM. 2020 Aug 21;:

Authors: F F, Mj W, D N

Abstract
Cystic fibrosis (CF) is the most common life-threatening inherited condition in the Caucasian population, where mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene result in a multifactorial syndrome, with pulmonary disease representing the largest contributor to morbidity and mortality. Life expectancy has improved and the recent development of disease-modifying CFTR modulator therapies is likely to further improve survival. However, increasing life expectancy brings new challenges related to the complications of a chronic disease including an increasing prevalence of cystic fibrosis related diabetes (CFRD), itself associated with increased morbidity and early mortality. This review provides an update as regards the underlying mechanisms, investigation and management of CFRD.

PMID: 32821951 [PubMed - as supplied by publisher]

Rapid and robust evolution of collateral sensitivity in Pseudomonas aeruginosa antibiotic-resistant mutants.

Sci Adv. 2020 Aug;6(32):eaba5493

Authors: Hernando-Amado S, Sanz-García F, Martínez JL

Abstract
The analysis of trade-offs, as collateral sensitivity, associated with the acquisition of antibiotic resistance, is mainly based on the use of model strains. However, the possibility of exploiting these trade-offs for fighting already resistant isolates has not been addressed in depth, despite the fact that bacterial pathogens are frequently antibiotic-resistant, forming either homogeneous or heterogeneous populations. Using a set of Pseudomonas aeruginosa-resistant mutants, we found that ceftazidime selects pyomelanogenic tobramycin-hypersusceptible mutants presenting chromosomal deletions in the analyzed genetic backgrounds. Since pyomelanogenic resistant mutants frequently coexist with other morphotypes in patients with cystic fibrosis, we analyzed the exploitation of this trade-off to drive extinction of heterogeneous resistant populations by using tobramycin/ceftazidime alternation. Our work shows that this approach is feasible because phenotypic trade-offs associated with the use of ceftazidime are robust. The identification of conserved collateral sensitivity networks may guide the rational design of evolution-based antibiotic therapies in P. aeruginosa infections.

PMID: 32821825 [PubMed - as supplied by publisher]

H1N1 Influenza Virus in Patients With Cystic Fibrosis: A Literature Review Examining Both Disease Entities and Their Association in Light of the 2009 Pandemic.

Cureus. 2020 Jul 16;12(7):e9218

Authors: Wiltshire DA, Vahora IS, Tsouklidis N, Kumar R, Khan S

Abstract
The novel coronavirus (COVID-19) that is challenging the health sector and negatively impacting the global economy takes us back to the 2009 influenza A (H1N1) virus pandemic that brought the world to a standstill. In 2009, H1N1 became a significant health concern for several months. It mainly affected people under the age of 65 hyears who had no prior immunity, including children. Among the high-risk populations were pregnant patients and those with chronic cardiac, pulmonary, or respiratory diseases. These patients were at risk of developing severe pneumonia and respiratory complications. Cystic fibrosis (CF) represents a form of severe chronic lung disease in young adults and is the major fatal hereditary disorder of Caucasians in the United States. An online search of PubMed and Google Scholar was conducted to find relevant literature that explicitly examines patients with CF and H1N1.

PMID: 32821569 [PubMed - as supplied by publisher]

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ENaC regulation by phospholipids and DGK explained through mathematical modeling.

Sci Rep. 2020 Aug 18;10(1):13952

Authors: Olivença DV, Voit EO, Pinto FR

Abstract
Cystic fibrosis is a condition caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). It is also thought to increase the activity of epithelial sodium channels (ENaC). The altered function of these ion channels is one of the causes of the thick dehydrated mucus that characterizes the disease and is partially responsible for recurrent pulmonary infections and inflammation events that ultimately destroy the lungs of affected subjects. Phosphoinositides are signaling lipids that regulate numerous cellular processes and membrane proteins, including ENaC. Inhibition of diacylglycerol kinase (DGK), an enzyme of the phosphoinositide pathway, reduces ENaC function. We propose a computational analysis that is based on the combination of two existing mathematical models: one representing the dynamics of phosphoinositides and the other explaining how phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) influences ENaC activity and, consequently, airway surface liquid. This integrated model permits, for the first time, a detailed assessment of the intricate interactions between DGK and ENaC and is consistent with available literature data. In particular, the computational approach allows comparisons of two competing hypotheses regarding the regulation of ENaC. The results strongly suggest that the regulation of ENaC is primarily exerted through the control of PI(4,5)P2 production by type-I phosphatidylinositol-4-phosphate 5-kinase (PIP5KI), which in turn is controlled by phosphatidic acid (PA), the product of the DGK reaction.

PMID: 32811866 [PubMed - in process]

The implementation of an aminoglycoside induced ototoxicity algorithm for people with cystic fibrosis.

J Cyst Fibros. 2020 Aug 15;:

Authors: Elson EC, Meier E, Oermann CM

Abstract
Aminoglycoside antibiotics treat respiratory infections in cystic fibrosis (CF). An aminoglycoside induced ototoxicity algorithm (AIOA) was implemented to assess ototoxicity among people with CF treated with intravenous and/or inhaled aminoglycosides. Prior to AIOA implementation, 14 of 52 patients (27%) treated with intravenous aminoglycosides had an audiogram. In the 24 months post AIOA implementation, 43 of 44 patients (98%) treated with intravenous aminoglycosides had an audiogram, with 27 (63%) demonstrating abnormalities. Prior to AIOA development, 18 of 70 patients (26%) who received at least two courses of inhaled aminoglycosides had an audiogram. Post AIOA implementation, 33 patients qualified for an audiogram after receiving inhaled aminoglycosides. Of these, 19 (58%) had an audiogram and 10 (53%) had abnormalities. Overall, we identified 46 (61%) people with CF with hearing abnormalities compared to 2.4% in the CF Foundation Patient Registry. This suggests an urgent need for CF programs to implement AIOAs.

PMID: 32811788 [PubMed - as supplied by publisher]

Effect of Concomitant Azithromycin and Tobramycin Use on Cystic Fibrosis Pulmonary Exacerbation Treatment.

Ann Am Thorac Soc. 2020 Aug 18;:

Authors: Cogen JD, Faino AV, Onchiri F, Gibson RL, Hoffman LR, Kronman MP, Rosenfeld M, Nichols DP

Abstract
RATIONALE: Pulmonary exacerbations (PEx) are associated with significant morbidity in people with cystic fibrosis (CF). Severe PEx are treated with IV antibiotics, including tobramycin. CF care guidelines recommend continuing chronic maintenance medications during PEx treatment. Azithromycin (AZM) is one of the most widely prescribed chronic medications for CF in the United States. Recent evidence has identified a potential antagonistic relationship between AZM and tobramycin.
OBJECTIVES: To determine if, among PEx treated with intravenous (IV) tobramycin, concomitant AZM use is associated with worse clinical outcomes.
METHODS: Retrospective cohort study utilizing the CF Foundation Patient Registry- Pediatric Health Information System (CFFPR-PHIS) linked dataset. People with CF age 6-21 years were included if hospitalized between 2006 and 2016 for a PEx. Inverse probability of treatment weighing was utilized to minimize the effects of confounders, including indication bias. Associations of concomitant treatment with AZM and lung function outcomes were determined using linear mixed effect models and generalized estimating equations. Cox proportional hazard regression models were used to evaluate associations with time to next PEx.
RESULTS: Among the 10,660 people with CF included in the CFFPR-PHIS linked dataset, 2,294 children and adolescents with 5,022 PEx that had IV tobramycin use were identified. A little less than half (N=2,247; 45%) of all PEx were treated concomitantly with AZM and IV tobramycin. AZM use both at the most recent outpatient clinic encounter and during PEx treatment in combination with IV tobramycin was associated with a significantly lower absolute improvement in percent predicted forced expiratory volume in 1 second (ppFEV1) (-0.93%, [95% CI -1.78, -0.07]; p=0.033), a lesser odds of returning to ≥90% of baseline ppFEV1 (OR 0.79, [95% CI 0.68, 0.93]; p=0.003), and a shorter time to next PEx requiring IV antibiotics (Hazard Ratio 1.22, [95% CI 1.14, 1.31]; p=<0.001) compared to IV tobramycin use without concomitant AZM.
CONCLUSIONS: Concomitant AZM and IV tobramycin use for in-hospital pediatric PEx treatment was associated with poorer clinical outcomes than treatment with IV tobramycin without AZM. These results support the hypothesis that an antagonistic relationship between these two medications might exist.

PMID: 32810412 [PubMed - as supplied by publisher]

Pharmacotherapeutic management of bronchial infections in adults: non-cystic fibrosis bronchiectasis and chronic obstructive pulmonary disease.

Expert Opin Pharmacother. 2020 Aug 18;:1-15

Authors: Di Pasquale M, Aliberti S, Mantero M, Gramegna A, Blasi F

Abstract
INTRODUCTION: Effective management of both acute and chronic bronchial infections is mandatory due to their high frequency rate, the relevant morbidity and mortality and the significant burden to health care systems, especially with the aging of population. Bacteria are the main causative pathogens, followed by viruses, and less commonly by fungi. The clinical evaluation of new therapeutic associations is mandatory to cope with the increases in resistance, in association with better infection control and antimicrobial policies.
AREAS COVERED: The authors searched Medline for any article published in English language up until March 1, 2020 that concerns the treatment of acute exacerbations and chronic infections in chronic obstructive respiratory disease and bronchiectasis.
EXPERT OPINION: As acute exacerbations are a main common and detrimental event in patients with COPD and bronchiectasis, effective antimicrobial therapies and regimens should be optimized. The development of new molecules or combination regimens is vital to patients with severe and/or difficult-to-treat infections. Moreover, chronic infection control is mandatory in these patients to their improve quality of life, respiratory function and prognosis as well as for reducing health care costs.

PMID: 32808825 [PubMed - as supplied by publisher]

Pharmacokinetics in Patients with Cystic Fibrosis: A Systematic Review of Data Published Between 1999 and 2019.

Clin Pharmacokinet. 2020 Aug 18;:

Authors: De Sutter PJ, Gasthuys E, Van Braeckel E, Schelstraete P, Van Biervliet S, Van Bocxlaer J, Vermeulen A

Abstract
BACKGROUND: Cystic fibrosis is a lethal inherited disease that affects multiple organs. To provide optimal pharmacological treatment of comorbidities associated with cystic fibrosis, relevant alterations in pharmacokinetics must be known.
OBJECTIVE: The objective of this study was to compare the pharmacokinetics of drugs between patients with cystic fibrosis and controls, based on clinical study reports published from 1999 to 2019.
METHODS: Clinical studies were considered if patients with cystic fibrosis and patients without cystic fibrosis/healthy volunteers were included, a drug was administered orally/intravenously and pharmacokinetic parameters were compared.
RESULTS: In total, 32 clinical studies were included. Twenty-one studies reported absorption parameters. For multiple drugs, speed and/or extent of oral absorption were lower in cystic fibrosis. This phenomenon is possibly related to pathophysiological changes in the gastrointestinal tract associated with cystic fibrosis. However, a large proportion of drugs had comparable absorption kinetics. Twenty-one studies discussed volume of distribution, which was comparable between groups for most drugs. Initial differences became smaller when scaled to body composition. For some highly protein-bound drugs, inflammation-related changes in plasma proteins helped explain residual variability between cystic fibrosis and controls. Twenty-four studies elaborated on clearance, whereby higher clearances were observed in cystic fibrosis. In contrast with previously published reviews, no evidence was found for increased activities of drug-metabolising enzymes nor for up-regulation of active transport processes involved in drug disposition. In most cases, scaling clearance parameters to body composition and/or incorporating differences in plasma protein concentration accounted for these larger clearances.
IMPLICATIONS: There is no evidence that genetic defects causing cystic fibrosis directly lead to altered pharmacokinetics. However, co-morbidities can have a potential impact on drug absorption and disposition. Because of gastrointestinal complications, it is not advisable to extrapolate drug absorption parameters from healthy volunteers to patients with cystic fibrosis. Differences observed in the volume of distribution and clearance in patients with cystic fibrosis can potentially be explained by correcting for lean body mass.

PMID: 32808233 [PubMed - as supplied by publisher]

Long-term safety study of colistimethate sodium (Colobreathe®): Findings from the UK Cystic Fibrosis Registry.

J Cyst Fibros. 2020 Aug 14;:

Authors: Kaplan S, Lee A, Caine N, Charman SC, Bilton D

Abstract
BACKGROUND: As part of the risk management plan in Europe, a long-term observational study was conducted to monitor the safety of colistimethate sodium dry powder for inhalation (CMS-DPI) compared to other inhaled antibiotics.
METHODS: A cohort of CMS-DPI patients and a matched cohort were identified from the UK Cystic Fibrosis Registry (UKCFR) from 2014-2018. The primary outcome was a composite endpoint, defined as adverse events (AEs) or new cystic fibrosis (CF) complications. Other outcomes included pulmonary exacerbations and treatment discontinuations.
RESULTS: Of 1466 and 3503 patients in the CMS-DPI and comparator cohorts, respectively, 82.7% and 79.4% had AEs. Among the most common new CF complications were osteopenia, CF-related diabetes, and increased liver enzymes. The adjusted event rate ratio (ERR) for the primary outcome was 1.25 (95% confidence interval [CI]: 1.18-1.33, p<0.001). After excluding new CF complications, there was no difference between cohorts (ERR=1.04, 95% CI: 0.79-1.38, p=0.785). Pulmonary exacerbations were common in CMS-DPI and comparator cohorts (78.0% and 79.9% of patients, respectively), with adjusted ERR of 1.02 (95% CI: 0.95-1.10, p=0.523). Rates of discontinuation were similar in the CMS-DPI and Tobramycin inhalation powder comparator cohorts (37.8% and 39.8% of patients, respectively).
CONCLUSIONS: There was no difference in the rate of adverse events between CMS-DPI and comparator cohorts. The safety profile of CMS-DPI is similar to those of other inhaled antibiotics, supporting its long-term safety in CF people with CF. The UKCFR has developed a successful model for partnership with industry to conduct long-term studies aimed at assessing drug safety.

PMID: 32807645 [PubMed - as supplied by publisher]

Correction to: Probiotics' efficacy in paediatric diseases: which is the evidence? A critical review on behalf of the Italian Society of Pediatrics.

Ital J Pediatr. 2020 Aug 17;46(1):116

Authors: Martinelli M, Banderali G, Bobbio M, Civardi E, Chiara A, D'Elios S, Lo Vecchio A, Olivero M, Peroni D, Romano C, Stronati M, Turra R, Viola I, Staiano A, Villani A

Abstract
An amendment to this paper has been published and can be accessed via the original article.

PMID: 32807216 [PubMed - in process]

Acute Malnutrition in Children: Pathophysiology, Clinical Effects and Treatment.

Nutrients. 2020 Aug 12;12(8):

Authors: Dipasquale V, Cucinotta U, Romano C

Abstract
Acute malnutrition is a nutritional deficiency resulting from either inadequate energy or protein intake. Children with primary acute malnutrition are common in developing countries as a result of inadequate food supply caused by social, economic, and environmental factors. Secondary acute malnutrition is usually due to an underlying disease causing abnormal nutrient loss, increased energy expenditure, or decreased food intake. Acute malnutrition leads to biochemical changes based on metabolic, hormonal, and glucoregulatory mechanisms. Most children with primary acute malnutrition can be managed at home with nutrition-specific interventions (i.e., counseling of parents, ensuring household food security, etc.). In case of severe acute malnutrition and complications, inpatient treatment is recommended. Secondary acute malnutrition should be managed by treating the underlying cause.

PMID: 32806622 [PubMed - in process]

Lysosomal Reacidification Ameliorates Vinyl Carbamate-Induced Toxicity and Disruption on Lysosomal pH.

J Agric Food Chem. 2020 Aug 07;:

Authors: Li Y, Hu D, Qi J, Cui S, Chen W

Abstract
Ethyl carbamate (EC) is a carcinogen toxicant, commonly found in fermented foods and beverages. The carcinogenic and toxic possibility of EC is thought to be related to its metabolite vinyl carbamate (VC). However, we found interesting mechanisms underlying VC-induced toxicity in this study, which were greatly different from EC. We first conducted a simple synthesis procedure for VC and found that VC possessed higher toxicity but failed to regulate levels of reactive oxygen species, glutathione, and autophagy. Notably, VC treatment resulted in upregulation of lysosomal pH, which was responsible for its cytotoxicity. Cyclic adenosine monophosphate (cAMP) pretreatment could enhance restoration of lysosomal acidity and ameliorate VC-induced damage. Inhibition of protein kinase A and cystic fibrosis transmembrane conductance regulator can block cAMP-induced cytoprotection. Together, our results provided the evidence for novel mechanisms of toxicity and possible protection method under VC exposure, which might give new perspectives on the study of EC-induced toxicity.

PMID: 32806125 [PubMed - as supplied by publisher]

StatPearls

Book. 2020 01

Authors:

Abstract
Nasal polyps are benign inflammatory and hyperplastic outgrowths of the sinonasal mucosa. Their most common manifestation is in patients with chronic rhinosinusitis (CRS). For this reason, the term chronic rhinosinusitis with nasal polyposis (CRSwNP) is frequently used when discussing the topic of nasal polyps. However, they are also associated with aspirin-exacerbated respiratory disease (AERD), certain systemic vasculitis, and cystic fibrosis, among others.[1] Presentation ranges from asymptomatic persons to patients with significant nasal obstruction, nasal and facial congestion, anosmia, ageusia, and rhinorrhea. These symptoms decrease the quality of life (QOL) of affected individuals.[2][3]

PMID: 32809581

StatPearls

Book. 2020 01

Authors:

Abstract
Spinal muscular atrophy (SMA) denotes a collection of inherited clinical syndromes causing degeneration of anterior horn cells in the spinal cord with associated destruction of alpha motor cells and presents clinically with characteristic proximal muscle weakness and atrophy.[1] Homozygous deletion at 5q13 (the coding region for the survival motor neuron (SMN1) gene) is responsible for 95% of cases of SMA, and after cystic fibrosis is the second most common cause of autosomal recessive inherited related mortality with an estimated incidence of 1 in 6000 to 11000.[2][3] Homozygous deletion at 5q13 is also referred to as classical proximal SMA and will be the focus of this article with differentials and other causes of SMA discussed below. SMA is heterogeneous in presentation and ranges from death within weeks of birth to mild proximal weakness developing during adulthood. Earlier presentations are typically associated with poorer function and prognosis: classification of SMA subtypes are determined by the age of onset as well as clinical severity and life expectancy.[4]  SMA was first described in the 1890s, first by Guido Werdnig in describing intermediate and severe SMA in 2 brothers and then 7 cases by Johan Hoffmann; type I SMA is sometimes eponymously referred to as Werdnig-Hoffmann disease. Similarly, milder forms of SMA (type III) detailed by Kugelberg and Welander is sometimes eponymously referred to as Kugelberg-Welander disease.[5]

PMID: 32809522

Rethinking bedtime resistance in children with autism: is restless legs syndrome to blame?

J Clin Sleep Med. 2020 Aug 17;:

Authors: Kanney ML, Durmer JS, Trotti LM, Leu R

Abstract
STUDY OBJECTIVES: In this study we investigated the clinical correlates of restless legs syndrome in children with autism and report on our experiences with response to treatment.
METHODS: A retrospective chart review of children seen in our sleep center from 2016-2019 was performed to identify children with autism and chronic insomnia. Patients underwent clinical assessments for restless legs symptomatology. Overnight polysomnogram, serum ferritin testing, and response to clinical treatment data were collected.
RESULTS: A total of 103 children with autism and chronic insomnia were identified (age range 2 - 19 years). Of these, 41 children (39%) were diagnosed with restless legs syndrome. The diagnosis of restless legs syndrome was associated with significantly lower serum ferritin levels (mean 29 ±18.62 ng/mL versus non-RLS 56.7 ± 17.59, P<0.001) and higher PLMS on PSG (8.12 ± 6.6 versus non-RLS 0.06 ±0.17). The presence of leg kicking, body rocking, or any symptoms involving the legs, highly correlated with the diagnosis of RLS. Positive treatment response was noted in nearly all treated patients, including those treated with oral iron supplementation alone (25 children, 23 responders), gabapentin alone (12 children, all responders), and combination therapy (3 children, all responders).
CONCLUSIONS: Our findings suggest restless legs syndrome may represent an underrecognized cause of insomnia in children with autism. Initial assessment should include a thorough query of behaviors related to nocturnal motor complaints, because restless legs syndrome may be a treatable cause of sleep disruption.

PMID: 32804073 [PubMed - as supplied by publisher]