Posterior reversible encephalopathy syndrome could be an underestimated variant of “reversible neurological deficits” in Systemic Lupus Erythematosus

Background

Posterior reversible encephalopathy syndrome (PRES) has been increasingly identified in patients with systemic lupus erythematosus (SLE) owing to the advance in neuroimaging techniques. Prompt diagnosis is pivotal to improve its outcome. To analyze the clinical and radiographic profile of PRES in patients with SLE and search for the appropriate treatment strategy PRES in SLE.

Methods

SLE patients who fulfilled the diagnostic criteria for PRES from August 2008 to January 2011 were evaluated at baseline, and followed to determine clinical outcomes. Data were analysis on clinical characteristics, laboratory abnormalities, treatment details, and outcomes.

Results

Ten episodes of PRES in patients with SLE were identified. All patients were female, mean age of onset was 22.93?±?2.48 years, and SLEDAI at the onset of PRES were 25.8?±?5.7. All cases had acute onset of headache, altered mental status, stupor, vomiting, cortical blindness and seizures. Neurological symptoms were the initial manifestation of SLE in three cases. Head magnetic resonance imaging (MRI) demonstrated posterior white matter edema involving the parietal, temporal and occipital lobes, which were more conspicuous on T2 weighted spin echo and diffusion-weighted MR imaging (DWI) than on computed tomography (CT) scan. Complete clinical and radiographic recovery was observed in 8 patients after prompt treatment with corticosteroids.

Conclusions

PRES might be due to lupus per se besides other traditional causative factors such as hypertension. PRES might be an underestimated variant of “reversible neurological deficits” in SLE. Prompt recognition and timely management is important to prevent permanent neurological deficits.

     

Clinical and Radiological Spectrum of Posterior Reversible Encephalopathy Syndrome: Does Age Make a Difference? – A Retrospective Comparison between Adult and Pediatric Patients

Background

Posterior reversible encephalopathy syndrome (PRES) is a serious and increasingly recognized disorder, but data from observational studies on clinicoradiological differences between etiologies and age groups are limited. In this study, we aimed to investigate the clinical and imaging characteristics of PRES in children compared to adults in a large cohort.

Methods

We retrospectively reviewed the radiological report data bases between January 1999 and August 2012 for patients with PRES (total of 110 patients). Patients fulfilling the criteria for PRES after detailed investigation of clinical charts and imaging studies were separated into children (<18years) and adults (≥18years). Various imaging features at onset of symptoms and on follow-up as well as clinical and paraclinical data were analyzed.

Results

A total of 19 pediatric and 91 adult patients with PRES were included into the study. In pediatric PRES patients, seizures were significantly more frequent as initial PRES-related symptom (p = 0.01). In addition, in children the superior frontal sulcus topographic lesion pattern occurred as frequent as the parieto-occipital one and was significantly more prevalent than in adults (p = 0.02). In contrast, in adults visual disturbances tended to occur more frequently than in children (p = 0.05). Also, severity of edema tended to be greater in adults than in children (p = 0.07).

Conclusion

In our PRES cohort, we found relevant clinicoradiological differences between pediatric and adult PRES patients. However, prospective studies are warranted to establish factors that are specifically associated with pediatric PRES.     

A three generations family with blepharo-naso-facial malformations suggestive of Pashayan syndrome

Blepharo-naso-facial syndrome, described by Pashayan et al. (10), is characterized by telecanthus, lateral displacement and stenosis of lacrimal puncta, bulky nose, mask-like facies, trapezo?dal upper lip, torsion dystonia and mental retardation. We report on a family with this rare malformation syndrome, confirming the existence of this syndrome and its dominant inheritance. The proband had a fleshy nose, a prominant nose bridge, an hypoplastic midface, telecanthus with temporal displacement of puncta, lacrimal excretory obstruction. CNS torsion dystonia, increased deep tendon reflexes, Babinski reflexes, poor coordination and joint laxity. The proband's mother, brother and maternal grandfather also showed manifestations of the syndrome. The proband and his brother had delayed developmental milestones. Hearing impairment was present in the proband, his mother and his grandfather but was absent in the proband's brother. The blepharonasofacial syndrome was described by Pashayan et al. (10) in four members of one family, two male and one female sib and their mother. Two other sibs were unaffected. Many of the features of the blepharo-facio-nasal syndrome also occur in other well known syndromes i.e. Waardenburg syndrome. The pedigrees of the family of Pashayan et al. (10) and of our family are compatible with Mendelian dominant inheritance, either autosomal or X-linked. X-linked dominant inheritance cannot be ruled out except by male-to-male transmission, which does not occur in these families. Pashayan et al. (10) suggested that an autosomal gene with variable expressivity appears more likely. More families are needed for defining the transmission of the condition and for mapping the gene involved in the blepharo-naso-facial syndrome.     

Fragile X tremor/ataxia syndrome: blame the messenger!

rCGG repeats in premutant alleles of the fragile X gene (FMR1) cause neurodegeneration in Drosophila and are thought to cause fragile X-associated tremor/ataxia syndrome in humans. Two reports in this issue of Neuron (Jin et al. and Sofola et al.) present data indicating a disease mechanism involving disruption of RNA-binding protein function.     

Determinants of Recovery from Severe Posterior Reversible Encephalopathy Syndrome

Objective

Few outcome data are available about posterior reversible encephalopathy syndrome (PRES). We studied 90-day functional outcomes and their determinants in patients with severe PRES.

Design

70 patients with severe PRES admitted to 24 ICUs in 2001–2010 were included in a retrospective cohort study. The main outcome measure was a Glasgow Outcome Scale (GOS) of 5 (good recovery) on day 90.

Main Results

Consciousness impairment was the most common clinical sign, occurring in 66 (94%) patients. Clinical seizures occurred in 57 (81%) patients. Median mean arterial pressure was 122 (105–143) mmHg on scene. Cerebral imaging abnormalities were bilateral (93%) and predominated in the parietal (93%) and occipital (86%) white matter. Median number of brain areas involved was 4 (3–5). Imaging abnormalities resolved in 43 (88%) patients. Ischaemic and/or haemorrhagic complications occurred in 7 (14%) patients. The most common causes were drug toxicity (44%) and hypertensive encephalopathy (41%). On day 90, 11 (16%) patients had died, 26 (37%) had marked functional impairments (GOS, 2 to 4), and 33 (56%) had a good recovery (GOS, 5). Factors independently associated with GOS<5 were highest glycaemia on day 1 (OR, 1.22; 95%CI, 1.02–1.45, p = 0.03) and time to causative-factor control (OR, 3.3; 95%CI, 1.04–10.46, p = 0.04), whereas GOS = 5 was associated with toxaemia of pregnancy (preeclampsia/eclampsia) (OR, 0.06; 95%CI, 0.01–0.38, p = 0.003).

Conclusions

By day 90 after admission for severe PRES, 44% of survivors had severe functional impairments. Highest glycaemia on day 1 and time to causative-factor control were strong early predictors of outcomes, suggesting areas for improvement.     

Tilorone confers robust in vitro and in vivo antiviral effects against severe fever with thrombocytopenia syndrome virus

Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging pathogen, is a tick-borne bunyavirus belonging to the genus Bandavirus in the family Phenuiviridae (Kuhn et al., 2020). This pathogen was first identified in China during the heightened surveillance of acute febrile illness in 2009, and has been reported to cause several outbreaks in eastern Asia areas, including China, Japan, and Korea (Yu et al., 2011). Besides, Vietnam has also reported several confirmed SFTS cases (Tran et al., 2019). The mortality rate in hospitalised patients with SFTSV infection is up to 10%–30%. Moreover, SFTSV has been reported to possibly transmitted by the contact of body fluids from person-to-person, and extensive SFTSV contamination was detected in the patient rooms (Kim et al., 2015). These reports suggest that more stringent isolation measures are needed for the prevention of massive SFTSV outbreak.     

Modeling Rett syndrome with stem cells

The discovery that somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) raised the exciting possibility of modeling diseases with patient-specific cells. Marchetto et?al. (2010) now use iPSC technology to generate, characterize, and treat an in?vitro model for the autism spectrum disorder Rett syndrome.     

Apparent Lenz microphthalmia syndrome: a patient with unusual manifestations

Lenz microphthalmia syndrome was first described by Lenz et al. in 1955 (9). The cardinal features of the syndrome are microphthalmia or anophthalmia, microcephaly, mental retardation, external ear, digital, cardiac, skeletal, dental and genitourinary anomalies. Here we present a case of Lenz microphthalmia syndrome that shows the typical characteristics and, additionally, macrophallus, a broad chest with widely spaced nipples, wide gap between first and second toes, which are unusual manifestations in Lenz Microphthalmia Syndrome.     

Comparison of four computerized models to estimate 24-hour growth hormone secretion in girls with Turner's syndrome.

Daily pituitary growth hormone (GH) secretion can be estimated from a 24-hour GH profile by various methods. We have used four methods to assess GH secretion in 36 girls with Turner's syndrome: the method described by Thompson et al., the Pulsar algorithm combined with the method of Hellman et al. and two deconvolution techniques. The number of detected peaks varied considerably among the methods. The mean (+/- SD) total daily secretion per square meter body surface was 0.53 (0.19) U/m2.day by deconvolution, in contrast to 0.31 (0.17) with the Hellman method and 1.06 (0.37) according to Thompson. The differences are explained by different assumptions about the metabolic clearance rate and various methodological aspects. Assuming a degradation rate of 50%, the growth hormone substitution dosage would be 1-2 IU/m2.day in GH-deficient children. The usual dosage in girls with Turner's syndrome is expected to lead to serum GH levels approximately 4 times higher than in the untreated state.     

Molecular deconvolution of the neutralizing antibodies induced by an inactivated SARS-CoV-2 virus vaccine

Dear Editor, The rapid emergence and persistence of the pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has had enormous impacts on global health and the economy.Effective vaccines against SARS-CoV-2 are urgently needed to control the coronavirus disease 2019(COVID-19) pandemic,and multiple vaccines have been found to be efficacious in preventing symptomatic COVID-19(Polack et al.,2020;Wu et al.,2020;Jones and Roy,2021).We have developed a traditional beta-propiolactone-inacti-vated aluminum hydroxide-adjuvanted whole-virion SARS-CoV-2 vaccine (BBIBP-CorV),which elicited protective immune responses in clinical trials (Wang et al.,2020;Xia et al.,2021).The vaccine has been granted conditional approvals or emergency use authorizations (EUAs) in China and other countries.     

Linkage mapping of a severe X-linked mental retardation syndrome.

A four-generation Swedish family with a new type of X-linked mental retardation syndrome was recently reported by Gustavson et al. The complex syndrome includes microcephaly, severe mental retardation, optical atrophy with decreased vision or blindness, severe hearing defect, characteristic facial features, spasticity, seizures, and restricted joint motility. The patients die during infancy or early in childhood. Twenty-one family members, including two affected males, were available for study. Linkage analysis was conducted in the family by using 11 RFLP markers and 10 VNTR markers spread along the X chromosome. A hypervariable short tandem repeat of DXS294 at Xq26 showed a peak two-point lod score of 3.35 at zero recombination fraction. Calculations using the same markers revealed a multipoint peak lod score of 3.65 at DXS294. Crossover events with the centromeric marker DXS424 and the telomeric marker DXS297 delimit a probable region for the gene localization. It is noteworthy that hte disease loci of two other syndromes with overlapping clinical manifestations recently were shown by Turner et al. and Pettigrew et al. to be linked to markers at Xq26.     

Usher syndrome type I is not linked to D1S81 (pTHH 33): evidence for genetic heterogeneity

Usher syndrome is an autosomal recessive disease associating congenital sensorineural deafness and retinitis pigmentosa. Two clinical forms have been recognized, namely a) congenital and severe (type I) and b) later and moderate (type II). A linkage of the D1S81 probe (THH 33) with the gene for type II has been recently demonstrated by Kimberling et al. 1990. Here, a panel of 29 individuals from 6 kindreds with Usher syndrome type I has been tested for possible allelism at the D1S81 locus. A negative lod-score was found with this probe and close linkage to this region could be excluded. These different results support the view that the clinical heterogeneity in Usher syndrome is accounted for by an obvious genetic heterogeneity.     

The ups and downs of BDNF in Rett syndrome

Rett syndrome (RTT) is an X-linked postnatal neurodevelopmental disorder, which is primarily caused by mutations in the gene encoding methyl-CpG binding protein 2 (MeCP2). A number of MeCP2 target genes have been identified, including the neurotrophic factor BDNF; however, the functional relevance of these targets has not been established. In this issue of Neuron, Chang et al. provide the first in vivo evidence for a functional interaction between BDNF and MeCP2.     

Diversity of metabolic syndrome risk factors in obese children and adolescents

The aim of this study was to investigate the frequency of metabolic syndrome (MS) variables in a group of spanish obese children and adolescents, to asses MS prevalence in this population and to describe it's relationship with other metabolic risk factors. 103 children were studied : 54 male and 49 female, mean age 10.08+/-2.3 with exogenous obesity. Obesity was defined when BMI was higher than the age and sex specific equivalent to 30 kg/m(2) in adults. MS variables considered were waist circumference, blood pressure, fasting blood triglycerides, fasting glucose/insulin and HDL-cholesterol. The children were considered as having the MS when three or more characteristics showed abnormal values according to Cook and De Ferranti definitions. HOMA index, ApoB and ApoA1 were studied too. The most frequent features of the metabolic syndrome were excess waist circumference and hypertension. The MS markers with the lowest frequency were dyslipidemia and fasting hyperglicemia. MS prevalence was 29,9% (Cook et al. criteria) and 50% (De Ferranti et al. criteria). Fasting insulin and HOMA index values increased significantly (p < 0.05) when three or more abnormalities of the MS variables were present. Apo B increased significantly only in females (p < 0.05) and Apo Al decreased significantly (p < 0.05) in both sexes when MS was present. Adequate metabolic syndrome risk factors criteria, mainly cut-off values, need to be defined in the European paediatric population.     

Integrity of the thyroglobulin locus in tricho-rhino-phalangeal syndrome II

Summary The thyroglobulin gene has been mapped to chromosome band 8q24 by several investigators. This is the band implicated in the causation of Langer-Giedion syndrome (tricho-rhino-phalangeal syndrome II). We have examined a restriction fragment length polymorphism at the thyroglobulin locus in a patient with Langer-Giedion syndrome and 8q deletion in order to: (1) localize the Langer-Giedion deletion more precisely, (2) define the relative map positions of the thyroglobulin gene and the Langer-Giedion locus. The results indicate that the locus of the thyroglobulin gene is intact in the patient with an interstitial deletion of proximal band 8q24.1 which confirms its more distal localization reported earlier by Bergé-Lefranc et al. (1985). It also assigns the critical region for the causation of Langer-Giedion syndrome to the proximal part of band 8q24, viz. 8q24.11q24.13.     

An electrifying iPSC disease model: long QT syndrome type 2 and heart cells in a dish

In a recent Nature paper, Itzhaki et?al. (2011) generate induced pluripotent stem cells (iPSCs) from patients with a potentially fatal inherited arrhythmia, long QT syndrome type 2. Cardiomyocytes differentiated from the patient-derived iPSCs exhibit the hallmark cardiac electrical signatures of the disease, which can be reversed by pharmacological intervention.     

Pan-coronavirus fusion inhibitors as the hope for today and tomorrow

The last two decades of the 21st century have seen emerging zoonotic coronavirus(CoV)diseases,including severe acute respiratory syndrome(SARS)(Holmes 2003),Middle East respiratory syndrome(MERS)(Graham et al.,2013)and coronavirus disease 2019(COVID-19)(Jiang et al.,2020).     

New powers of brown fat: fighting the metabolic syndrome

An understanding of the full powers of brown adipose tissue (BAT) is only successively being accumulated. In a paper in Nature Medicine, Bartelt et al. (2011) add further impressive aspects to the potential powers of BAT in the combat against the metabolic syndrome by demonstrating its vast capacity for triglyceride clearance and glucose disposal.     

Model selection for integrated recovery/recapture data

Catchpole et al. (1998, Biometrics 54, 33-46) provide a novel scheme for integrating both recovery and recapture data analyses and derive sufficient statistics that facilitate likelihood computations. In this article, we demonstrate how their efficient likelihood expression can facilitate Bayesian analyses of these kinds of data and extend their methodology to provide a formal framework for model determination. We consider in detail the issue of model selection with respect to a set of recapture/recovery histories of shags (Phalacrocorax aristotelis) and determine, from the enormous range of biologically plausible models available, which best describe the data. By using reversible jump Markov chain Monte Carlo methodology, we demonstrate how this enormous model space can be efficiently and effectively explored without having to resort to performing an infeasibly large number of pairwise comparisons or some ad hoc stepwise procedure. We find that the model used by Catchpole et al. (1998) has essentially zero posterior probability and that, of the 477,144 possible models considered, over 60% of the posterior mass is placed on three neighboring models with biologically interesting interpretations.     

Microbial carboxylic ester hydrolases (EC 3.1.1) in food biotechnology

Ester linkages between carboxylic acid groups and hydroxyl groups are basic to the structure of carboxyesters and lipids, and occur commonly as modifications of polysaccharide molecules. Microorganisms produce enzymes which hydrolyse the carboxylic ester linkages in substrates which are being utilized for growth. Such esterase reactions are frequently easily reversible, depending on the concentration of reactants or availability of water. The importance of esters as flavour compounds has resulted in the selection of yeast strains which produce esters in beverage fermentation. The synthetic potential of triacylglycerol lipases (EC 3.1.1.3) has been exploited by use of the purified enzymes in environments of low water activity. The techniques of molecular biology facilitate analysis of the homology between carboxylesterase enzymes and a detailed knowledge of structure and specificity provides the opportunity to modify enzymes to suit particular applications in biotechnology.
Esterase activity can be assayed conveniently by using synthetic chromogenic esters of naphthol or nitrophenol. Naphthyl and nitrophenyl acetates are readily hydrolysed by a wide range of enzymes including lipases (Hofelmann et al. 1985; Brahimi-Horn et al. 1990; Gilbert et al. 1991), serine protease (Klapper et al. 1973) and acetylxylan esterase (Lee et al. 1987). Electrophoretic separation followed by detection using chromogenic esters has demonstrated polymorphism of esterase enzymes and has been used to type strains of bacteria (Goullet & Picard 1990, 1991; Picard & Goullet 1990) but was less discriminating with yeasts (Campbell et al. 1972) and edible mushrooms (Itavaara 1988).