关键词： health-related quality of life   neurologically impaired   cochlear implantation  

摘要： Objectives Evaluate health-related quality-of-life (HRQoL) measures in noncommunicative, neurologically impaired, developmentally delayed (NCNIDD) children compared to normally developing children (ND) who undergo cochlear implantation (CI). Study Design Cross-sectional survey of parents of NCNIDD and ND children who underwent CI. Setting Two tertiary care medical centers. Methods Questions comprising the Children With Cochlear Implants: Parental Perspectives survey were used in analysis. Average responses were calculated within 8 domains (communication, general functioning, self-reliance, well-being and happiness, social relationships, education, effects of implantation, and support the child). Groups were compared using Wilcoxon rank-sum test. Impact of individual and collective socioeconomic/family covariates was assessed using analysis of variance. Results Surveys were returned from 17 of 42 (40%) patients with NCNIDD and 35 of 131 (27%) patients with ND. There were no statistically significant differences between groups in survey response rate, age, sex, age at implantation, current age, or duration of implant use. Overall, parents of children with ND responded more favorably in all domains vs children with NCNIDD. Parents of children with NCNIDD answered neutrally or favorably in all domains, except "support the child" and "self-reliance" domains. Differences between groups in mean domain scores, univariably and almost universally when adjusting for socioeconomic and family variables individually and collectively, were statistically significant. Conclusions This study suggests that HRQoL benefits of CI are perceived in most domains by parents of children with NCNIDD, albeit less strongly than children with ND. A survey sensitive to challenges of children with NCNIDD may better capture benefits that may not be apparent in this study.

关键词： complication   gastroesophageal reflux disease   gastrostomy   neurological impairment   prognostic nutritional index  

摘要： Background Neurological impairment (NI) is responsible for most conditions that require a permanent gastrostomy tube. The present study assessed the occurrence of short- and long-term complications after video-assisted gastrostomy (VAG) in patients with NI. Methods The incidence of short- (<6 months) and long-term (over 2 years) complications of VAG were analyzed in a retrospective study. The differences between the incidence of the complications of VAG according to the age at surgery (<= 15 years vs. >= 16 years) were also evaluated. The short- and long-term complications observed were granulation tissue formation, infection requiring antibiotic treatment, skin problems, perigastrostomy leakage, vomiting, accidental tube dislodgement, dumping syndrome, ileus, and peritonitis. Results Eighty-two patients were evaluated for short- and long-term complications. The long-term complication rate was significantly lower than the short-term complication rate (P = 0.0026). Onodera's prognostic nutritional index before VAG in patients with long-term complications was significantly lower than in patients without such complications (P = 0.046). The incidence of long-term granulation tissue formation, infection, and vomiting were significantly lower than those of similar short-term complications. Long-term skin problems were associated with short-term skin problems (odds ratio: 18.95;95% confidence interval: 4.53-92.98;P < 0.001). The number of patients >= 16 years old with short- and long-term skin problems was significantly higher than in patients <= 15 years old (P = 0.0014 and P = 0.0073, respectively). Conclusions The incidence rate of granulation tissue formation and infection after VAG were lower in the long term than in the short term. However, patients >= 16 years old presented with persistent complications.

关键词： COVID-19   Neuroimmunology   Cerebrovascular disease   Critical illness  

摘要： Coronavirus Disease 2019 is predominantly a disorder of the respiratory system, but neurological complications have been recognised since early in the pandemic. The major pathophysiological processes leading to neurological damage in COVID-19 are cerebrovascular disease, immunologically mediated neurological disorders and the detrimental effects of critical illness on the nervous system. It is still unclear whether direct invasion of the nervous system by the Severe Acute Respiratory Syndrome Coronavirus 2 occurs;given the vast numbers of people infected at this point, this uncertainty suggests that nervous system infection is unlikely to represent a significant issue if it occurs at all. In this review, we explore what has been learnt about the neurological complications of COVID-19 over the course of the pandemic, and by which mechanisms these complications most commonly occur.

关键词： cerebrotendinous xanthomatosis   clinical heterogeneity   neurological involvement   newborn screening   tendon xanthomas  

摘要： Background Cerebrotendinous xanthomatosis (CTX) is an autosomal recessively inherited inborn error of metabolism. Neurological symptoms are considered to be a clinical hallmark of untreated adult patients. We describe a 'milder CTX phenotype', without neurological involvement. Methods We performed a retrospective patient file study in 79 genetically confirmed Dutch patients with CTX (55 patients aged >= 21 years) to study the clinical heterogeneity of CTX. We studied the frequency of adult patients with CTX without neurological involvement at diagnosis, in our Dutch cohort, and included a family from South Africa and patients from Italy, USA, Chile and Asia from the literature. Results In total, we describe 19 adult patients with CTX from 16 independent families, without neurological symptoms at diagnosis. A relatively small percentage (21%, n = 4) had a history of cataract. The majority, 84% (n = 16), presented with tendon xanthomas as the sole or predominant feature. The majority of patients showed increased plasma cholesterol levels. No correlation was found between this 'milder phenotype', the cholestanol levels and the CYP27A1 genotype. In addition, we describe three novel mutations in the CYP27A1 gene. Conclusions This study shows the clinical heterogeneity of CTX, highlighting the existence of a 'milder phenotype', that is without neurological involvement at diagnosis. Adult patients with CTX may present with tendon xanthomas as the sole or predominant feature, mimicking familial hypercholesterolemia. It is important to realize that the absence of neurological symptoms does not rule out the development of future neurological symptoms. As CTX is a treatable disorder, early diagnosis and initiation of treatment when additional clinical signs occur is therefore essential.

关键词： Congenital nephrotic syndrome   Genetics   Galloway-Mowat syndrome   Pierson syndrome   Charcot-Marie-Tooth   Microcephaly  

摘要： Genetic studies of hereditary nephrotic syndrome (NS) have identified more than 50 genes that, if mutated, are responsible for monogenic forms of steroid-resistant NS (SRNS), either isolated or syndromic. Most of these genes encode proteins expressed in the podocyte with various functions such as transcription factors, mitochondrial proteins, or enzymes, but mainly structural proteins of the slit diaphragm (SD) as well as cytoskeletal binding and regulator proteins. Syndromic NS is sometimes associated with neurological features. Over recent decades, various studies have established links between the physiology of podocytes and neurons, both morphologically (slit diaphragm and synapse) and functionally (signaling platforms). Variants in genes expressed in different compartments of the podocyte and neurons are responsible for phenotypes associating kidney lesions with proteinuria (mainly Focal and Segmental Glomerulosclerosis (FSGS) or Diffuse Mesangial Sclerosis (DMS)) and central and/or peripheral neurological disorders. The Galloway-Mowat syndrome (GAMOS, OMIM#251300) associates neurological defects, microcephaly, and proteinuria and is caused by variants in genes encoding proteins of various functions (microtubule cytoskeleton regulation (WDR73), regulation of protein synthesis via transfer RNAs (KEOPS and WDR4 complexes)). Pierson syndrome (OMIM#609049) associating congenital nephrotic syndrome and central neurological and ophthalmological anomalies is secondary to variants in LAMB2, involved in glomerular and ocular basement membranes. Finally, Charcot-Marie-Tooth-FSGS (OMIM#614455) combines peripheral sensory-motor neuropathy and proteinuria and arises from INF2 variants, resulting in cytoskeletal polymerization defects. This review focuses on genetic syndromes associating nephrotic range proteinuria and neurological involvement and provides the latest advances in the description of these neuro-renal disorders.

关键词： miR-29a   Intracerebral hemorrhage   Axonal outgrowth   PTEN   Neurological function  

摘要： Spontaneous intracerebral hemorrhage (ICH) is a clinical challenge with high disability and lacks an effective treatment. miR-29a strongly expressed in the brain has been implicated in various neurological disorders. In this study, we investigated the biological roles of miR-29a in axonal outgrowth and neurological outcomes after ICH and relevant molecular mechanism. The rat model of ICH was established by injection of autologous whole blood into the right basal ganglia. First, a significant decrease in miR-29a level was found in perihematomal brain tissues and cerebrospinal fluid (CSF) after ICH in vivo and hemin-treated neurons in vitro. Further study documented that lentivirus-mediated miR-29a overexpression could remarkably attenuate hemorrhagic brain injury, promoted regenerative outgrowth of injured axons and improved neurobehavioral and cognitive impairments after ICH in rats. In addition, we also identified that overexpression of miR-29a obviously alleviated neuronal damage and mitochondrial dysfunctions, and facilitated neurite outgrowth in cultured neurons exposed to hemin in vitro. Furthermore, luciferase reporter assay showed that miR-29a directly targeted the 3 '-UTR region of phosphatase and tensin homolog (PTEN) mRNA and negatively regulated its expression. More importantly, pharmacological inhibition of PTEN has similar neuroprotective effects as miR-29a overexpression involving activation of the PI3K/Akt pathway after hemorrhagic stroke. Collectively, these results suggested that elevated miR-29a could contribute to axonal outgrowth and neurological recovery through targeting PTEN/PI3K/Akt pathway after ICH, thereby providing a potential therapeutic target for patients with ICH.

关键词： Podcasting   COVID-19   Medical education  

摘要： Background As medical education shifted to a virtual environment during the early coronavirus disease 2019 (COVID-19) pandemic, we evaluated how neurology podcasting may have been utilized during this period, and which features of podcasts have been more highly sought by a medical audience. Methods We conducted a retrospective analysis of neurology-themed blogs and/or podcasts between April 2019 and May 2020. Programs were eligible if they reported mean monthly downloads > 2000, were affiliated with an academic society, or offered continuing medical education credit. Thirty-day download counts were compared between study months, with adjustment for multiple testing. Exploratory analyses were performed to determine which podcast features were associated with higher downloads. Results Of the 12 neurology podcasts surveyed, 8 completed the survey and 5 met inclusion criteria. The median monthly download count was 2865 (IQR 869-7497), with significant variability between programs (p < 0.001). While there was a 358% increase in downloads during April 2020 when compared to the previous month, this was not significant (median 8124 [IQR 2913-14,177] vs. 2268 [IQR 540-6116], p(adj) = 0.80). The non-significant increase in overall downloads during April 2020 corresponded to an increase in unique episodes during that month (r = 0.48, p = 0.003). There was no difference in 30-day downloads among episodes including COVID-19 content versus not (median 1979 [IQR 791-2873] vs. 1171 [IQR 405-2665], p = 0.28). Conclusions In this unique, exploratory study of academic neurology-themed podcasts, there was no significant increase in episode downloads during the early COVID-19 pandemic. A more comprehensive analysis of general and subspecialty medical podcasts is underway.

关键词： Brain   Infant   Malaria   Neurodevelopment   Sub-Saharan Africa  

摘要： Objective: To compare neurological functioning of neonates born to mothers with and without malaria in pregnancy. Methods: Pregnant women presenting at Korle Bu Teaching Hospital, Ghana were recruited into this prospective observational study. Malaria exposure was determined by clinically documented antenatal malaria infection;parasitemia in maternal, placental, or umbilical cord blood;or placental histology. Neurological functioning was assessed using the Hammersmith Neonatal Neurological Examination within 48 hours of birth. Performance was classified as "optimal" or "suboptimal" by subdomain and overall. Results: Between November 21, 2018 and February 10, 2019, a total of 211 term-born neonates, of whom 27 (13%) were exposed to malaria in pregnancy, were included. In the reflexes subdomain, exposed neonates tended to score lower (adjusted mean difference-0.34, 95% confidence interval-0.70 to 0.03), with an increased risk (adjusted risk ratio 1.63, 95% confidence interval 1.09 to 2.44) of suboptimal performance compared with unexposed neonates. There were no significant between-group differences in scores or optimality classification for the remaining subdomains and overall. Conclusions: Malaria-exposed neonates had similar neurological functioning relative to unexposed neonates, with differences confined to the reflexes subdomain, suggesting potential underlying neurological immaturity or injury. Further studies are needed to confirm these findings and determine the significance of malaria in pregnancy on long-term neurological outcomes. (c) 2021 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://***/licenses/by-nc-nd/4.0/ )

关键词： Out-of-hospital cardiac arrest   Heart arrest   Emergency medical services  

摘要： Background: There is substantial regional variation in out-of-hospital cardiac arrest (OHCA) survival. We investigated whether regional emergency medical services (EMS) intra-arrest transport (IAT) practices are associated with patient outcomes. Methods: We performed a secondary analysis of a multi-center North American clinical trial dataset, which enrolled EMS-treated adult OHCA cases from 49 regional population-based clusters. The exposure of interest was regional-level intra-arrest transport (IAT), calculated as the proportion of cases in each cluster transported to hospital prior to return of spontaneous circulation, examined as quartiles and as a continuous variable. Multilevel mixed-eects logistic regression modeling estimated the association between regional IAT with survival to hospital discharge and favorable neurologic status (modified Rankin Scale < 3) at hospital discharge. Results: Of 26,148 subjects (median age 68 years;36% female;23% shockable initial rhythm) 2424 (9.3%), survived to hospital discharge and 1993 (7.6%) had favourable neurological outcomes. Across regional clusters, IAT ranged from 0.84% to 75% (quartiles <6.2%, 6.2-19.6%, 19.6-30.4%, and >30.4%). For each quartile, 13.3%, 7.9%, 7.4%, and 4.8% survived, and 10.4%, 7.8%, 7.4%, and 4.8% had favourable neurological status. Regional IAT (per 10% change) was associated with decreased probability of survival (AOR 0.86, 95% CI 0.82-0.91) and favorable neurological outcome (AOR 0.80, 95% CI 0.76-0.85). Conclusion: Treatment within a region that utilizes IAT less frequently was associated with improved clinical outcomes at hospital discharge. These findings may account for some of the known regional variation in OHCA outcomes.