Aicardi-Goutières syndrome (AGS).

In 1984, Jean Aicardi and Fran?oise Goutières described 8 children showing both severe brain atrophy and chronic cerebrospinal fluid lymphocytosis, with basal ganglia calcification in at least one member of each affected family. The course was rapid to death or a vegetative outcome. Aicardi and Goutières correctly predicted that the disorder would be genetic, but emphasised that "some features, especially the pleocytosis, may erroneously suggest an inflammatory condition". The increased interferon-alpha in affected children (Pierre Lebon, Paris) mimicked congenital viral infection, but the associated chilblains (pernio) pointed to lupus erythematosus and an autoimmune mechanism. Genetic research led by Yanick Crow has clarified these puzzling relationships in Aicardi-Goutières syndrome, a syndrome that now includes conditions previously known as microcephaly-intracranial calcification syndrome, pseudo-TORCH and Cree encephalitis. At the time of writing, Crow's team has discovered that over 80% of families with Aicardi-Goutières syndrome have mutations in one of four nuclease genes, the exonuclease TREX1 and the genes for all three subunits of the ribonuclease H2 enzyme complex. Aicardi-Goutières syndrome is both genetically and phenotypically heterogeneous, with a range of severity from life-threatening perinatal illness to mild late infancy onset. All infants of whatever genotype have increased interferon-alpha in the first year of life and this appears to be the final common pathway that links Aicardi-Goutières syndrome, congenital virus infection and systemic lupus erythematosus.     

Aicardi-Goutières syndrome presenting atypically as a sub-acute leukoencephalopathy.

Aicardi-Goutières syndrome is an autosomal recessive encephalopathy characterised by acquired microcephaly, basal ganglia calcifications, leukodystrophy, cerebral atrophy, chronic cerebrospinal lymphocytosis, and raised titres of interferon alpha in the cerebrospinal fluid. The disease onset is generally within the first months of life. We here report a case of Aicardi-Goutières syndrome presenting atypically as a sub-acute leukoencephalopathy following satisfactory psychomotor development up to the age of 16 months. This case highlights the importance of considering Aicardi-Goutières syndrome in the differential diagnosis of an unexplained leukoencephalopathy and the possibility of later onset of the disease.     

The neuropathology of Aicardi-Goutières syndrome

Aicardi-Goutières syndrome is an autosomal recessive neurodegenerative disorder with unique characteristics which include cerebrospinal fluid lymphocytosis, cytokine involvement (interferon-alpha in plasma and in cerebrospinal fluid), a unique distribution of cerebral calcifications, and early loss of myelin. Surprisingly only a very small number of detailed neuropathological studies are available. This paper summarizes the findings. Calcifications are both present as concretions and as perivascular cuffs of calcium surrounding small vessels. Small vessel involvement (microangiopathy) is apparent from a typical distribution of microinfarctions in at least one case studied. Together with signs of extracerebral vascular involvement known from earlier reports this finding points to microangiopathy as an important pathogenic mechanism in Aicardi-Goutières syndrome.     

Systemic inflammatory response syndrome

Systemic inflammatory response syndrome is a term used to describe the host's response to infection or diffuse tissue injury characterized by the release of various proinflammatory and antiinflammatory mediators. The local release of inflammatory mediators is critical in the development of a systemic inflammatory response. If the initial response is balanced and contained, homeostasis is preserved. However, if either response is excessive, systemic involvement and end organ damage occur. Understanding the relationships between the initiators and secondary mediators generated in response to inflammation improves our understanding of the clinical syndrome associated with infection and progressive multiple system organ dysfunction. It also creates a potential role for the use of cytokines in early diagnosis of infection and development of targeted therapeutic strategies to attenuate the systemic inflammatory response and improve clinical outcome. Copyright © 2001 by W.B. Saunders Company     

Aicardi-Goutières-Syndrom

Aicardi-Goutières syndrome (AGS) is a rare severe progressive encephalopathy which starts in early infancy. Hallmarks include calcifications of the basal ganglia, chronic lymphopleocytosis and abnormal interferon-α elevations in cerebrospinal fluid (CSF). The disorder mimicks intrauterine infections, but is a genetic disorder, mostly inherited by an autosomal recessive trait with a variable genetic and clinical spectrum. In clinical and laboratory presentation, there is an overlap to infantile systemic lupus erythematosus. Four different genes have been identified to date, others are assumed. They code for nucleases, which are involved in cellular repair mechanisms by cleaving RNA-DNA particles. Mutations cause, via enzyme inactivation, a chronic overstimulation of the innate immune system, leading to increased CSF interferon-α production. Prenatal diagnosis is available for known mutations.     

Aicardi-Goutières�ۺ���

??Aicardi-Goutières syndrome??AGS?? is a rare group of genetically determined disorders mainly with neurological and skin involvement. The main clinical features include multiple intracranial calcification??white matter changes??chronic lymphocytosis in cerebrospinal fluid??CSF????chilblains or other skin lesions. Seven pathogenic genes have been identified??including TREX1??RNASEH2B??RNASEH2C??RNASEH2A??SAMHD1??ADAR1 and IFIH1. This article will comprehensively discuss AGS in its pathogenesis??clinical manifestations??auxiliary examination??diagnosis and differential diagnosis??therapies and prognosis.     

重症肠道病毒71型感染患儿胃肠功能损害的诊治

危重手足口病患儿可出现脑干脑炎、脑脊髓炎、肺水肿/肺出血和心血管功能衰竭等严重合并症.部分患儿合并严重胃肠功能损害,表现为腹胀、肠麻痹、便血、呕血等胃肠动力学障碍或消化道出血等症状."儿茶酚胺风暴"和病毒性炎症反应可能是胃肠功能障碍的主要原因,应重视对胃肠损害的监测.胃肠功能障碍的防治以预防为主,并应注意避免医源性损害.

Abstract：

Severe hand, foot and mouth disease (HFMD) may lead to the high mortality due to brainstem encephalitis, encephalomyelitis, pulmonary edema/pulmonary hemorrhage and cardiopulmonary failure in children. Some patients are complicated with severe gastrointestinal dysfunction, manifested as abdominal distension, intestinal paralysis, bleedy stool, haematemesis. "Catecholamine storm" and viral systemic inflammatory response syndrome may be the main mechanisms for gastrointestinal dysfunction. It is important to focus on the monitoring of gastrointestinal dysfunction of severe HFMD. Preventing and avoiding iatrogenic damage of gastrointestinal dysfunction are main treatment strategies.     

Aicardi-Goutières syndrome: a description of 21 new cases and a comparison with the literature

The International Aicardi-Goutières Syndrome Association (IAGSA) was founded in 2000, its aim being to collect and analyse all available information on this rare syndrome (whose true incidence is not known) in order to increase knowledge of the pathology and the number of reported cases. We analysed the clinical, neuroradiological and biological characteristics of 21 new Aicardi-GoutiÉres syndrome subjects (seven observed directly and 14 on whom we gathered detailed clinical information) and compared our findings with data in the literature. The main clinical symptoms (pyramidal and extrapyramidal symptoms, psychomotor delay, microcephaly) and neuroradiological features (basal ganglia calcification, atrophy, white matter alterations) observed show a greater homogeneity in our subjects than in the literature cases, which indicates an improvement in the diagnostic accuracy of Aicardi-Goutières syndrome. Other symptoms, such as feeding difficulties and irritability are less frequent, but characteristic and present early (even at onset of the disease). In the literature, doubts are expressed as to whether lymphocytosis and/or raised interferon-alpha in cerebrospinal fluid are crucial for a diagnosis of Aicardi-GoutiÉres syndrome. Our data suggest that they are, and in particular that an important role is played by raised interferon-alpha. The clinical course seems to show different stages: early onset, rapid progression, severe deterioration, stabilization. Our follow-up seems to indicate a trend not necessarily towards a worsening, but instead towards a stabilization or even a slight improvement of the clinical picture.     

Bleeding ears: case report of Munchausen syndrome by proxy

ABSTRACT. A two and a half year old child presented with "bleeding'ears which proved to be factitious in origin. A previous episode of haematuria, haematemesis and melaena at age 9 months was probably also factitious. A brief discussion of Munchausen syndrome by proxy is presented.     

Group B Streptococcus late-onset disease presenting as cellulitis-adenitis syndrome

Cellulitis-adenitis syndrome is a rare clinical manifestation of group B Streptococcus (GBS) late-onset disease. Its significance lies in the fact that local infection may be the only initial sign of systemic infection that is often concurrent with meningitis. Soft tissue involvement (cellulitis-adenitis) can sometimes be the only initial manifestation of GBS infection. We report four cases of GBS cellulitis-adenitis syndrome from different hospitals in Barcelona and Tarragona. We emphasize that early diagnosis and treatment may improve the potentially poor prognosis of these patients, and stress the need to rule out central nervous system involvement by studying cerebrospinal fluid.     

Systematic review on fecal calprotectin in cystic fibrosis

ObjectivesFecal calprotectin is an inflammatory marker used for monitoring intestinal diseases. It has been studied as a marker of intestinal inflammation in cystic fibrosis (CF), a multi-systemic genetic disease caused by alterations to the CFTR gene. Manifestations of the disease favor a systemic inflammation not limited to the respiratory tract, therefore, calprotectin is a non-invasive and effective diagnostic method. The aim of the study was to perform a systematic review of the literature with a qualitative synthesis of studies.SourcesThe articles were selected from PubMed, Web of Science, Scielo and Lilacs.Summary of the findingsNine studies were selected for that qualitative synthesis, one was a randomized clinical trial, and eight were case-control or cohort designs. Most studies have indicated that calprotectin is a marker of systemic inflammation in CF and not just intestinal inflammation. Calprotectin is an aid in monitoring inflammatory bowel conditions in patients with cystic fibrosis.ConclusionFurther studies should be conducted to investigate the role of this marker in the systemic inflammation of CF.     

A case of relapsing flitting bilateral idiopathic orbital inflammation

Idiopathic orbital inflammation (IOI) is defined as a benign non-infective clinical syndrome characterized by features of non-specific inflammation of the orbit without identifiable local or systemic causes. This can be called orbital myositis if the inflammation is predominantly in the orbital muscles. It is a diagnosis of exclusion based on clinical, radiological, and if necessary, histological findings. The most commons symptoms are swelling, ptosis, proptosis and painful eye movements. To our knowledge, this patient is the first with IOI to demonstrate relapsing flitting bilateral involvement of several individual extra-ocular muscles.     

Inflammation and pre-eclampsia

Pre-eclampsia is a common and potentially dangerous disorder of human pregnancy. The maternal syndrome of hypertension, proteinuria and oedema is part of a severe systemic inflammatory response that includes leukocyte and endothelial cell activation. Although the origins of pre-eclampsia remain unclear, a major cause is the failure to develop an adequate blood supply to the placenta, leading to placental oxidative stress. This results in the excess release of placental factors, such as syncytiotrophoblast debris or soluble fms-like tyrosine kinase-1 (sFlt-1), the soluble receptor for vascular endothelial growth factor (VEGF), into the maternal circulation, where they trigger an inflammatory response and endothelial dysfunction. Alternatively, pre-eclampsia can develop in the presence of a normal placenta in women that are susceptible to systemic inflammation, such as with chronic cardiovascular disease or diabetes. While clinical management of pre-eclampsia does not currently include anti-inflammatory agents, current research is focusing on ways to reduce inflammation and oxidative stress.     

Pediatric gastritis and peptic ulcer disease

Inflammation of the gastric and duodenal mucosa is the end result of an imbalance between mucosal defensive and aggressive factors. The degree of inflammation and imbalance between defensive and aggressive factors can then result in varying degrees of gastritis and/or mucosal ulceration. Gastritis and ulcers of the duodenum or stomach can be classified as primary or secondary. The majority of children with chronic gastritis and ulcers in the stomach or duodenum have secondary inflammation or mucosal ulceration. These secondary ulcers generally occur due to a systemic condition like head trauma or overwhelming sepsis, or as sequelae to drug ingestion (i.e. non-steroidal anti-inflammatory agents), but secondary gastroduodenal ulcers can also occur in specific disease conditions such as Zollinger-Ellison syndrome or Crohn’s disease. In almost all children with primary duodenal or gastric ulcers mucosal inflammation and, less frequently, ulceration is caused by a spiral shaped, gram-negative, microaerobic rodHelicobacter pylori. Recent epidemiological evidence has linked chronicH. pylori infection with the development of gastric carcinomas.     

Coagulation, inflammation, and the risk of neonatal white matter damage

Indicators of coagulation activation are sometimes increased in the blood of newborns and adults who have a systemic inflammatory response. These coagulation factors have the ability to exacerbate inflammation, which in turn can promote coagulation. Therapies directed solely at coagulation factors and therapies directed solely at inflammation factors have not proved effective in reducing mortality in adults with a systemic inflammatory response syndrome and multi-organ dysfunction (SIRS/MOD). On the other hand, the only therapy that has reduced mortality in SIRS/MOD is activated protein C, which has both anti-coagulation and anti-inflammatory effects. This and other observations support the view that activated coagulation factors enhance inflammation. Since newborns at risk of cerebral white matter damage and cerebral palsy are more likely than their peers to have a systemic inflammatory response, which is sometimes accompanied by elevated blood levels of coagulation factors, we suggest that activated coagulation factors contribute to the occurrence of cerebral white matter damage by exacerbating inflammatory phenomena, rather than by occluding cerebral blood vessels.     

Inflammation-induced preterm lung maturation: lessons from animal experimentation

Intrauterine inflammation, or chorioamnionitis, is a major contributor to preterm birth. Prematurity per se is associated with considerable morbidity and mortality resulting from lung immaturity but exposure to chorioamnionitis reduces the risk of neonatal respiratory distress syndrome (RDS) in preterm infants. Animal experiments have identified that an increase in pulmonary surfactant production by the preterm lungs likely underlies this decreased risk of RDS in infants exposed to chorioamnionitis. Further animal experimentation has shown that infectious or inflammatory agents in amniotic fluid exert their effects on lung development by direct effects within the developing respiratory tract, and probably not by systemic pathways. Differences in the effects of intrauterine inflammation and glucocorticoids demonstrate that canonical glucocorticoid-mediated lung maturation is not responsible for inflammation-induced changes in lung development. Animal experimentation is identifying alternative lung maturational pathways, and transgenic animals and cell culture techniques will allow identification of novel mechanisms of lung maturation that may lead to new treatments for the prevention of RDS.     

2‘,5’-oligoadenylate synthetase activity and T cell subset in the cerebrospinal fluid and peripheral blood of aseptic meningitis

2′,5′-oligoadenylate synthetase activity, which is assumed to be induced by interferon, is reported to be one of the useful markers reflecting interferon activity. The enzyme activity of patients with aseptic meningitis and febrile convulsion were compared in order to evaluate interferon activity as one of the local immuno-defense mechanisms of aseptic meningitis. The surface antigen of mononuclear cells in cerebrospinal fluid and peripheral blood of some patients with aseptic meningitis was also measured. The enzyme activity of patients with aseptic meningitis was 191.4 pmol/dL in the cerebrospinal fluid and 395.8 pmol/dL in the serum during the acute phase, while that of patients with febrile convulsion was 45.2 pmol/dL in the cerebrospinal fluid and 326.0 pmol/dL in the serum. The enzyme activity of the former patients significantly decreased during the recovery phase in both the cerebrospinal fluid and serum. CD3 positive cells in the peripheral blood were 56.3% of the total mononuclear cells during the acute phase and 65.2% during the recovery phase, whereas in the cerebrospinal fluid mononuclear cells, they were 87.1 and 85.5%, respectively. During the acute phase, CD4 positive cells were the predominant T lymphocyte subset in the cerebrospinal fluid cells, while CD8 positive cells were predominant during the recovery phase. The relative proportions of CD4 positive and CD8 positive cells during the acute and recovery phase in the cerebrospinal fluid mononuclear cells were quite high compared to the recovery phase, although that ratio of peripheral blood mononuclear cells was not changed throughout the course. It was concluded that T lymphocytes and increased 2′,5′-oligoadenylate synthetase activity in the cerebrospinal fluid may be one of the important components in the local inflammatory process independent of the systemic host defense mechanism in aseptic meningitis.     

Investigation of suspected Guillain–Barre syndrome in childhood: What is the role for gadolinium enhanced magnetic resonance imaging of the spine?

Aim: To review the role of gadolinium‐enhanced magnetic resonance imaging of the spine in the diagnosis of paediatric Guillain–Barre syndrome and compare it with nerve conduction studies and cerebrospinal fluid analysis. Methods: A retrospective review of investigations undertaken in children admitted to our institution with acute Guillain–Barre syndrome over a 10‐year period was performed. Results: Seven of eight children (88%) displayed post‐gadolinium nerve root enhancement consistent with Guillain–Barre syndrome. This compared with supportive nerve conduction studies in 21/24 children (88%) and cerebrospinal fluid protein analysis consistent with the diagnosis in 16/20 children (80%). Conclusion: Nerve conduction studies are the recognised ‘gold standard’ technique for confirming a clinical diagnosis of Guillain–Barre syndrome. In this study, a high positive rate was demonstrated. While more experience is necessary, this study and the literature support gadolinium enhanced magnetic resonance imaging of the spine as a valuable, although not necessarily superior, investigation in the diagnosis of Guillain–Barre syndrome. It may be of particular benefit when specialist neurophysiology expertise is unavailable.     

Cerebrospinal fluid shunts in the management of behavioural problems in Sanfilippo syndrome (MPS III)

Severe behavioural disturbance is a very common feature of Sanfilippo syndrome (mucopolysaccharidosis III, MPSIII), and one of the more difficult aspects of the disease to treat. We describe a series of six patients with MPS III who had cerebrospinal shunts inserted in an attempt to ameliorate behaviour that had proved refractory to conventional treatment. Symptoms improved significantly in all six but removal of the shunt was necessitated in one patient due to shunt blockage and infection. Conclusion Our experience suggests cerebrospinal fluid shunting should be formally evaluated as an adjunct to conventional forms of treatment of extreme behavioural disturbance in MPS III. Received: 14 October 1997 / Accepted: 25 February 1998     

Fatal haematemesis in childhood associated with aorto-oesophageal fistula

A case of fatal haematemesis associated with a non-traumatic, non-tuberculous aorto-oesophageal fistula in a 9-year-old Nigerian boy is presented. Autopsy revealed two inflamed and ulcerated mild-oesophageal pulsion diverticula, one of which had eroded into the right pleura as a sinus track. The second diverticulum had perforated and caused mediastinitis and eventually aorto-oesophageal fistula which led to the fatal haematemesis. A mild chest injury is seen as a precipitating factor of the haematemesis and not the initiator of the pathology.