Genetic, Phenotypic, and Interferon Biomarker Status in ADAR1-Related Neurological Disease

International audienceWe investigated the genetic, phenotypic, and interferon status of 46 patients from 37 families with neurological disease due to mutations in ADAR1. The clinicoradiological phenotype encompassed a spectrum of Aicardi–Goutières syndrome, isolated bilateral striatal necrosis, spastic paraparesis with normal neuroimaging, a progressive spastic dystonic motor disorder, and adult-onset psychological difficulties with intracranial calcification. Homozygous missense mutations were recorded in five families. We observed a p.Pro193Ala variant in the heterozygous state in 22 of 23 families with compound heterozygous mutations. We also ascertained 11 cases from nine families with a p.Gly1007Arg dominant-negative mutation, which occurred de novo in four patients, and was inherited in three families in association with marked phenotypic variability. In 50 of 52 samples from 34 patients, we identified a marked upregulation of type I interferon-stimulated gene transcripts in peripheral blood, with a median interferon score of 16.99 (interquartile range [IQR]: 10.64–25.71) compared with controls (median: 0.93, IQR: 0.57–1.30). Thus, mutations in ADAR1 are associated with a variety of clinically distinct neurological phenotypes presenting from early infancy to adulthood, inherited either as an autosomal recessive or dominant trait. Testing for an interferon signature in blood represents a useful biomarker in this context

Genetic, Phenotypic, and Interferon Biomarker Status in ADAR1-Related Neurological Disease

We investigated the genetic, phenotypic, and interferon status of 46 patients from 37 families with neurological disease due to mutations in ADAR1. The clinicoradiological phenotype encompassed a spectrum of Aicardi–Goutières syndrome, isolated bilateral striatal necrosis, spastic paraparesis with normal neuroimaging, a progressive spastic dystonic motor disorder, and adult-onset psychological difficulties with intracranial calcification. Homozygous missense mutations were recorded in five families. We observed a p.Pro193Ala variant in the heterozygous state in 22 of 23 families with compound heterozygous mutations. We also ascertained 11 cases from nine families with a p.Gly1007Arg dominant-negative mutation, which occurred de novo in four patients, and was inherited in three families in association with marked phenotypic variability. In 50 of 52 samples from 34 patients, we identified a marked upregulation of type I interferon-stimulated gene transcripts in peripheral blood, with a median interferon score of 16.99 (interquartile range [IQR]: 10.64–25.71) compared with controls (median: 0.93, IQR: 0.57–1.30). Thus, mutations in ADAR1 are associated with a variety of clinically distinct neurological phenotypes presenting from early infancy to adulthood, inherited either as an autosomal recessive or dominant trait. Testing for an interferon signature in blood represents a useful biomarker in this context

Integrating conservation objectives into forest management: coppice management and forest habitats in Natura 2000 sites

Most forest habitats, as defined and listed for their nature conservation importance in the Habitats Directive of the European Union and in the Bern Convention, result from centuries of human intervention. This paper explores the scope for, and the attitudes towards coppicing in Natura 2000 sites in some of the EU28 countries where coppice was historically one of the most important traditional silvicultural systems. A questionnaire survey was circulated to experts involved with Natura 2000 sites and case studies were conducted in Belgium, the Czech Republic, Estonia, Germany, Italy and the United Kingdom, to investigate attitudes to coppice silviculture within the framework of Natura 2000 site management plans. A list of forest habitat types capable of being managed as coppices was compiled and populated with sites at national and regional levels. At the regional level, management plans for the relevant forest habitat types in Natura 2000 sites were critically scrutinised together with other statutory, administrative or contractual measures. The results show that approaches to integrate coppice management into conservation plans differ widely. Examples of disparities are given and the possible causes discussed. A case is made for coppicing to be continued, where appropriate, as an important strategy in site management plans that aim to conserve habitats and improve forest biodiversity

Integrating conservation objectives into forest management: coppice management and forest habitats in Natura 2000 sites

Most forest habitats, as defined and listed for their nature conservation importance in the Habitats Directive of the European Union and in the Bern Convention, result from centuries of human intervention. This paper explores the scope for, and the attitudes towards coppicing in Natura 2000 sites in some of the EU28 countries where coppice was historically one of the most important traditional silvicultural systems. A questionnaire survey was circulated to experts involved with Natura 2000 sites and case studies were conducted in Belgium, the Czech Republic, Estonia, Germany, Italy and the United Kingdom, to investigate attitudes to coppice silviculture within the framework of Natura 2000 site management plans. A list of forest habitat types capable of being managed as coppices was compiled and populated with sites at national and regional levels. At the regional level, management plans for the relevant forest habitat types in Natura 2000 sites were critically scrutinised together with other statutory, administrative or contractual measures. The results show that approaches to integrate coppice management into conservation plans differ widely. Examples of disparities are given and the possible causes discussed. A case is made for coppicing to be continued, where appropriate, as an important strategy in site management plans that aim to conserve habitats and improve forest biodiversity

Pediatric epilepsy following neonatal seizures symptomatic of stroke

Background: Neonatal seizures are a risk factor for later epilepsy and their etiology is known to be implicated in the outcome but, little is known about this issue in the subgroup of seizures symptomatic of perinatal arterial ischemic stroke. The aim of this study was to describe the long term risk of epilepsy after electroencephalographic confirmed neonatal seizures symptomatic of perinatal arterial ischemic stroke. Design/subject: Fifty-five patients with electroclinical ictal data, vascular territory confirmed by neuroimaging and a minimum follow up of 3.5 years were identified from a multi-centre prospective neonatal seizures registry. Primary outcome was occurrence of post-neonatal epilepsy. The association of outcome with family history of epilepsy, gender, location of the infarct, neonatal clinical and electroencephalogram data were also studied. Results: During a mean follow up of 8 years and 5 months, 16.4% of the patients developed post neonatal epilepsy. The mean age at first post neonatal seizure was 4 years and 2 months (range 1-10 years and 6 months). Location of the infarct was the only statistically significant risk factor (p = 0.001); epilepsy was more represented in males but the difference was not statistically significant. Conclusions: Neonatal seizures symptomatic of perinatal arterial ischemic stroke had lower risk and later onset of post-neonatal epilepsy, compared to seizures described in the setting of other perinatal brain insults. Our data have implications for counseling to the family at discharge from neonatal intensive care unit. (c) 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved