We present a case report of a 13-year-old girl with Andersen-Tawil Syndrome (ATS), a rare genetic disorder which is characterized by dysmorphic features, ventricular arrhythmias, and frequent ...episodes of muscle paralysis that interfere with daily activities and social engagement. After the introduction of off-label treatment with acetazolamide periods without paralysis lengthened, our patient became more independent of the help of her parents and required a wheelchair less frequently, thus improving her social life. Based on our experience, we recommend a trial of acetazolamide in patients with ATS.
Aicardi-Goutières syndrome (AGS) is a genetically determined early-onset progressive encephalopathy caused by mutations leading to overexpression of type I interferon (IFN) and resulting in various ...clinical phenotypes. A gain-of-function (GOF) mutation in the
gene is associated with robust production of type I IFN and activation of the Janus kinase (JAK) signal transducer and activator of the transcription (STAT) pathway, which can cause AGS type 7. We detail the clinical case of an infant who initially presented with
pneumonia (PCP), had recurrent respiratory infections, and was later treated with a JAK inhibitor, baricitinib, because of a genetically confirmed GOF mutation in the
gene. This spectrum of
GOF mutations with overlapping features of hyperinflammation and severe opportunistic infection, which mimics combined immunodeficiency (CID), has not been described before. In this case, therapy with baricitinib effectively blocked IFN-α activation and reduced STAT1 signaling but had no effect on the progression of the neurological disease.
In children requiring electroencephalography (EEG), sleep recording can provide crucial information. As EEG recordings during spontaneous sleep are not always possible, pharmacological sleep-inducing ...agents are sometimes required. The aim of the study was to evaluate safety and efficacy of melatonin (Mel) and dexmedetomidine (Dex; intranasal and sublingual application) for sleep induction prior to EEG.
In this prospective randomized study, 156 consecutive patients aged 1-19 years were enrolled and randomized by draw into melatonin group (Mel;
= 54; dose: 0.1 mg/kg), dexmedetomidine (Dex) sublingual group (DexL;
= 51; dose: 3 mcg/kg) or dexmedetomidine intranasal group (DexN;
= 51; dose: 3 mcg/kg). We compared the groups in several parameters regarding efficacy and safety and also carried out a separate analysis for a subgroup of patients with complex behavioral problems.
Sleep was achieved in 93.6% of participants after the first application of the drug and in 99.4% after the application of another if needed. Mel was effective as the first drug in 83.3% and Dex in 99.0% (
< 0.001); in the subgroup of patients with complex developmental problems Mel was effective in 73.4% and Dex in 100% (
< 0.001). The patients fell asleep faster after intranasal application of Dex than after sublingual application (
= 0.006). None of the patients had respiratory depression, bradycardia, desaturation, or hypotension.
Mel and Dex are both safe for sleep induction prior to EEG recording in children. Dex is more effective compared to Mel in inducing sleep, also in the subgroup of children with complex behavioral problems.
Dexmedetomidine and Melatonin for Sleep Induction for EEG in Children, NCT04665453.
Spinalni disrafizmi so prirojene nepravilnosti hrbtenjače in spinalnega kanala, ki nastanejo zaradi motenj zapiranja nevralne cevi v zgodnjem embrionalnem razvoju. Glede na kožno kritje jih delimo na ...odprte in zaprte. Odprte disrafizme prepoznamo že s prenatalno diagnostiko, težja pa je prepoznava zaprtih (okultnih) stanj. Pri slednjih so nam pri diagnostiki v pomoč določeni kožni znaki nad hrbtenico, ki so prisotni pri več kot polovici bolnikov. Ultrazvočna preiskava spinalnega kanala je v prvih mesecih starosti, dokler hrbtenica ne zakosteni, metoda izbire v diagnostiki okultnih spinalnih disrafizmov. Sicer je najobčutljivejše diagnostično orodje magnetno resonančno slikanje, ki predstavlja tudi zlati standard predoperativne diagnostike. Zgodnja prepoznava je pomembna tudi v primerih asimptomatskih stanj, ker s tem omogočimo pravočasno kirurško zdravljenje otrok, pri katerih obstaja večje tveganje za nastanek nenadnih zapletov ali nepovratnih nevroloških posledic. V članku smo povzeli klinične in radiološke značilnosti posameznih disrafičnih stanj, ter oblikovali diagnostični algoritem, z namenom poenotenja zgodnje obravnave otrok s spinalnim disrafizmom.
Mechanisms of radiation-induced brain injury are not yet fully understood. Early failure oc-curs because of the eect of ionizing radiation on dividing endothelial cells and oligodendrocytes. ...Hypothetically, late radiation-induced brain injury is caused by chronic inammation and oxidative stress. In the case of irradiation of the hippocampus, the failure of neurogenesis and cognitive decline could be consequences of such pathological mechanisms. Due to the lack of diagnostic tools that could more precisely dene the brain injury aer irradiation, any therapy that may prevent such consequences in patients who require radiotherapy is currently not known. This article summarizes research hypotheses regarding processes of the brain damage aer radiation, prospects in the diagnosis and therapeutic approaches.
Spinal dysraphisms are congenital malformations of the spinal cord and spine that occur due to impaired closure of the neural tube in early embryogenesis. According to the skin coverage, they are ...divided into open and closed types. While open dysraphisms can be identified by prenatal investigations, the diagnosis of a closed (occult) dysraphic state is more difficult to establish. There are specific skin signs over the spine in more than half of these patients, which can help with early diagnosis. Ultrasonography of the spine and spinal cord is the method of choice in the diagnostics of occult spinal dysraphism in the first months of life, until the spine is closed. The most sensitive diagnostic tool is magnetic resonance imaging, which also represents the gold standard of preoperative diagnostics. Early diagnosis is important in asymptomatic conditions, as this allows timely surgical treatment of children, who are at greater risk of sudden onset of complications or neurological sequelae. In the article, we summarised clinical and radiological characteristics of dysraphic conditions and formed a diagnostic algorithm to unify an approach in a child with spinal dysraphism in the first months of life.
Mechanisms of radiation-induced brain injury are not yet fully understood . Early failure occurs because of the effect of ionizing radiation on dividing endothelial cells and oligodendrocytes. ...Hypothetically, late radiation-induced brain injury is caused by chronic inflammation and oxidative stress . In the case of irradiation of the hippocampus, the failure of neurogenesis and cognitive decline could be consequences of such pathological mechanisms. Due to lack of diagnostic tools, that could not more precisely define the brain injury after radiation, therapy, that may prevent such consequences in patients who require radiotherapy, is not currently known. This article summarizes research hypotheses regarding processes of the brain damage after radiation, prospects in the diagnosis and therapeutic approaches.
Pathogenic variants in DNA-damage regulated autophagy modulator 2 gene (DRAM2) cause a rare autosomal recessive retinal dystrophy and its disease course is not well understood. We present two ...Slovenian patients harboring a novel DRAM2 variant and a detailed review of all 23 other patients described to date. Whole exome and whole genome sequencing were performed in the two patients, and both underwent ophthalmological examination with a 2-year follow-up. PubMed was searched for papers with clinical descriptions of DRAM2 retinopathy. Patient 1 was homozygous for a novel variant, p.Met1?, and presented with the acute onset of photopsia and retina-wide retinopathy at the age of 35 years. The patient was first thought to have an autoimmune retinopathy and was treated with mycophenolate mofetil, which provided some symptomatic relief. Patient 2 was compound heterozygous for p.Met1? and p.Leu246Pro and presented with late-onset maculopathy at the age of 59 years. On review, patients with DRAM2 retinopathy usually present in the third decade with central visual loss, outer retinal layer loss on optical coherence tomography and a hyperautofluorescent ring on fundus autofluorescence. Either cone–rod or rod–cone dystrophy phenotype is observed on electroretinography, reflecting the importance of DRAM2 in both photoreceptor types. Non-null variants can result in milder disease.
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As variance from standard phospholipids of eubacteria and eukaryotes, archaebacterial diether phospholipids contain branched alcohol chains (phytanol) linked to glycerol exclusively with ether bonds. ...Giant vesicles (GVs) constituted of different species of archaebacterial diether phospholipids and glycolipids (archaeosomes) were prepared by electroformation and observed under a phase contrast and/or fluorescence microscope. Archaebacterial lipids and different mixtures of archaebacterial and standard lipids formed GVs which were analysed for size, yield and ability to adhere to each other due to the mediating effects of certain plasma proteins. GVs constituted of different proportions of archaeal or standard phosphatidylcholine were compared. In nonarchaebacterial GVs (in form of multilamellar lipid vesicles, MLVs) the main transition was detected at T(m) = 34. 2°C with an enthalpy of ΔH = 0.68 kcal/mol, whereas in archaebacterial GVs (MLVs) we did not observe the main phase transition in the range between 10 and 70°C. GVs constituted of archaebacterial lipids were subject to attractive interaction mediated by beta 2 glycoprotein I and by heparin. The adhesion constant of beta 2 glycoprotein I-mediated adhesion determined from adhesion angle between adhered GVs was in the range of 10(-8) J/m(2). In the course of protein mediated adhesion, lateral segregation of the membrane components and presence of thin tubular membranous structures were observed. The ability of archaebacterial diether lipids to combine with standard lipids in bilayers and their compatibility with adhesion-mediating molecules offer further evidence that archaebacterial lipids are appropriate for the design of drug carriers.
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