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The Korean Journal of Parasitology Mar 2012Congenital Neospora caninum infection was diagnosed in two Saanen goat kids from two distinct herds with a history of abortion and weak newborn goat kids in the Southern...
Congenital Neospora caninum infection was diagnosed in two Saanen goat kids from two distinct herds with a history of abortion and weak newborn goat kids in the Southern region of the State of Minas Gerais, Brazil. The first kid was weak at birth, had difficulty to rise and was unable to nurse. Gross lesions of porencephaly and hydrocephalus ex vacuo were seen. Multifocal necrosis, gliosis and non-supurative encephalitis were observed in the brain. Several parasitic cysts with a thick wall that reacted strongly only with polyclonal antiserum to Neospora caninum were seen in the cerebral cortex, brain stem and cerebellum. The second kid was born from a Neospora caninum seropositive mother that aborted in the last pregnancy. It was born without clinical signs. The diagnosis of neosporosis was based on antibody titer of 1:800 to N. caninum by indirect fluorescence antibody test obtained from blood collected before the goat kid ingested the colostrum and Neospora caninum DNA was detected by polymerase chain reaction and sequenced from placenta. This is the first report of neosporosis in goats in the southeast region of Brazil.
Topics: Animals; Antibodies, Protozoan; Brazil; Coccidiosis; Female; Goat Diseases; Goats; Molecular Sequence Data; Neospora; Pregnancy
PubMed: 22451736
DOI: 10.3347/kjp.2012.50.1.63 -
European Journal of Human Genetics :... Aug 2012Familial porencephaly, leukoencephalopathy and small-vessel disease belong to the spectrum of disorders ascribed to dominant mutations in the gene encoding for type IV...
Familial porencephaly, leukoencephalopathy and small-vessel disease belong to the spectrum of disorders ascribed to dominant mutations in the gene encoding for type IV collagen alpha-1 (COL4A1). Mice harbouring mutations in either Col4a1 or Col4a2 suffer from porencephaly, hydrocephalus, cerebral and ocular bleeding and developmental defects. We observed porencephaly and white matter lesions in members from two families that lack COL4A1 mutations. We hypothesized that COL4A2 mutations confer genetic predisposition to porencephaly, therefore we sequenced COL4A2 in the family members and characterized clinical, neuroradiological and biochemical phenotypes. Genomic sequencing of COL4A2 identified the heterozygous missense G1389R in exon 44 in one family and the c.3206delC change in exon 34 leading to frame shift and premature stop, in the second family. Fragmentation and duplication of epidermal basement membranes were observed by electron microscopy in a c.3206delC patient skin biopsy, consistent with abnormal collagen IV network. Collagen chain accumulation and endoplasmic reticulum (ER) stress have been proposed as cellular mechanism in COL4A1 mutations. In COL4A2 (3206delC) fibroblasts we detected increased rates of apoptosis and no signs of ER stress. Mutation phenotypes varied, including porencephaly, white matter lesions, cerebellar and optic nerve hypoplasia and unruptured carotid aneurysm. In the second family however, we found evidence for additional factors contributing to the phenotype. We conclude that dominant COL4A2 mutations are a novel major risk factor for familial cerebrovascular disease, including porencephaly and small-vessel disease with reduced penetrance and variable phenotype, which might also be modified by other contributing factors.
Topics: Adolescent; Adult; Animals; Apoptosis; Base Sequence; Basement Membrane; Brain; Brain Diseases; Child; Child, Preschool; Collagen Type IV; Consanguinity; Endoplasmic Reticulum Stress; Exons; Female; Genetic Predisposition to Disease; Hemiplegia; Heterozygote; Humans; Infant; Intracranial Aneurysm; Magnetic Resonance Imaging; Male; Mice; Mice, Knockout; Mutation; Pedigree; Porencephaly; Skin; Young Adult
PubMed: 22333902
DOI: 10.1038/ejhg.2012.20 -
American Journal of Human Genetics Jan 2012Porencephaly is a neurological disorder characterized by fluid-filled cysts or cavities in the brain that often cause hemiplegia. It has been suggested that...
Porencephaly is a neurological disorder characterized by fluid-filled cysts or cavities in the brain that often cause hemiplegia. It has been suggested that porencephalic cavities result from focal cerebral degeneration involving hemorrhages. De novo or inherited heterozygous mutations in COL4A1, which encodes the type IV α1 collagen chain that is essential for structural integrity for vascular basement membranes, have been reported in individuals with porencephaly. Most mutations occurred at conserved Gly residues in the Gly-Xaa-Yaa repeats of the triple-helical domain, leading to alterations of the α1α1α2 heterotrimers. Here we report on two individuals with porencephaly caused by a heterozygous missense mutation in COL4A2, which encodes the type IV α2 collagen chain. Mutations c.3455G>A and c.3110G>A, one in each of the individuals, cause Gly residues in the Gly-Xaa-Yaa repeat to be substituted as p.Gly1152Asp and p.Gly1037Glu, respectively, probably resulting in alterations of the α1α1α2 heterotrimers. The c.3455G>A mutation was found in the proband's mother, who showed very mild monoparesis of the left upper extremity, and the maternal elder uncle, who had congenital hemiplegia. The maternal grandfather harboring the mutation is asymptomatic. The c.3110G>A mutation occurred de novo. Our study confirmed that abnormalities of the α1α1α2 heterotrimers of type IV collagen cause porencephaly and stresses the importance of screening for COL4A2 as well as for COL4A1.
Topics: Amino Acid Sequence; Base Sequence; Brain Diseases; Child; Collagen Type IV; Female; Hemiplegia; Humans; Infant; Male; Molecular Sequence Data; Mutation, Missense; Pedigree; Porencephaly
PubMed: 22209246
DOI: 10.1016/j.ajhg.2011.11.016 -
Neurologia (Barcelona, Spain) Oct 2012To present 16 patients with schizencephaly and neurological involvement, and analyse their characteristics and neuroimages.
OBJECTIVE
To present 16 patients with schizencephaly and neurological involvement, and analyse their characteristics and neuroimages.
MATERIAL AND METHODS
The study included 16 patients, 8 males and 8 females, all of whom were diagnosed with schizencephaly at less than 3 years of age; 2 patients were diagnosed prenatally. Schizencephaly was identified by computerized tomography (CT) in 1 patient and by MR or three-dimensional MR (3DMR) with a 1.5tesla apparatus in the others. Most patients were referred for evaluation because of psychomotor delay, motor disabilities and/or seizures.
RESULTS
Five patients had bilateral schizencephaly with open lips (2 of them had suffered intrauterine cytomegalovirus infections); 2 showed unilateral schizencephaly with separated lips, 8 presented unilateral schizencephaly with fused lips, and 1 had schizencephaly with open lips on one side and fused lips on the other. Prenatal cytomegalovirus infection was diagnosed in 2 patients. A cerebral malformation that affected the midline was diagnosed by routine ultrasound studies in 2 patients. Eight patients (50%) presented with seizures that were focal, except for one patient who showed secondary generalisation. The latter was the only patient whose disease was refractory to complete seizure control with antiepileptic medication. All patients had some degree of motor deficit, which was either unilateral (hemiparesis) or bilateral (tetraparesis).
CONCLUSION
3D MR imaging was very important in diagnosing of schizencephaly in our patients because it showed the polymicrogyria that covered the area of the cleft and permitted us to rule out porencephaly. Neuronal migration disorders such as heterotopias and, more frequently, cortical dysplasias, were observed in several patients. Half of the patients had epilepsy which was controlled with antiepileptic medication, except in 1 patient.
Topics: Child, Preschool; Developmental Disabilities; Electroencephalography; Female; Head; Humans; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Infant; Infant, Newborn; Magnetic Resonance Imaging; Male; Malformations of Cortical Development; Tomography, X-Ray Computed
PubMed: 21890242
DOI: 10.1016/j.nrl.2011.06.005 -
Archivos Argentinos de Pediatria Jun 2011Misoprostol is commonly used in Argentina to attempt abortion, although a certain proportion of pregnancies is not interrupted. On the other hand, various reports showed...
INTRODUCTION
Misoprostol is commonly used in Argentina to attempt abortion, although a certain proportion of pregnancies is not interrupted. On the other hand, various reports showed an association between misoprostol and congenital anomalies.
OBJECTIVES
To estimate the risk of major congenital anomalies in children prenatally exposed to misoprostol, and to know their way of consumption during pregnancy.
METHOD
A cohort study compared the frequency of abortion and major congenital abnormalities in offspring of pregnant women exposed to misoprostol (94) and an unexposed group of pregnant women (401), both groups consulting to a teratology information service.
RESULTS
Among women exposed to misoprostol only the 8.2% purchased it on prescription, 81.5% heard about its abortifacient effect by friends, neighbors or relatives, the average dose was 1.439 μg which was used both orally and vaginally by the 77.2%; the mean gestational age was 48.5 days and 35.2% used an additional abortive agent. Women exposed to misoprostol had a significantly higher frequency of abortions (exposed: 17/94= 18.1%, unexposed, 29/401= 7.2%, RR= 2.27, 95%: 1,30-3,98), and offspring with major congenital abnormalities (exposed: 5/77= 6.49%, unexposed: 8/372= 2.15%, RR= 3.02, 95%:1,02-8.98). The five malformed children prenatally exposed to misoprostol showed: 1) encephalocele and transverse limb defects; 2) porencephaly, 3) pulmonary adenomatous cystic malformation, 4) occipital encephalocele and, 5) intestinal malrotation.
CONCLUSIONS
The study found a significant association between prenatal exposure to misoprostol and the occurrence of major congenital anomalies.
Topics: Abnormalities, Drug-Induced; Abortifacient Agents, Nonsteroidal; Adult; Argentina; Female; Humans; Misoprostol; Pregnancy; Prospective Studies
PubMed: 21660388
DOI: 10.1590/S0325-00752011000300007 -
Revista de Neurologia May 2011
Topics: Brain; Brain Diseases; Collagen Type IV; Hemiplegia; Humans; Magnetic Resonance Imaging; Malformations of Cortical Development; Porencephaly
PubMed: 21488010
DOI: No ID Found -
BMC Psychiatry Mar 2010Malformations of the cerebral cortex are often associated with developmental delay and psychoses. Porencephaly is a rare congenital disorder of central nervous system... (Review)
Review
BACKGROUND
Malformations of the cerebral cortex are often associated with developmental delay and psychoses. Porencephaly is a rare congenital disorder of central nervous system involving a cyst or a cavity filled with cerebrospinal fluid, in brain's parenchyma.
CASE PRESENTATION
We present a 25 years old woman with her first psychotic episode. She also suffers from porencephaly in the frontotemporal lobes region. It is emphasized that the two consistently abnormal brain regions in schizophrenia research had significant damage in this patient since birth. There is a total of only five cases of schizencephaly or porencephaly associated with psychosis in the scientific literature. Their clinical characteristics as well as the imaging results are described.
CONCLUSION
It is unclear if porencephaly and psychosis concur by chance or are causally related. The area where the porencephalic cysts appear seems to be of relevance. This case highlights the need for further research.
Topics: Adult; Central Nervous System Cysts; Comorbidity; Female; Functional Laterality; Humans; Magnetic Resonance Imaging; Malformations of Cortical Development; Psychotic Disorders; Radiography; Schizophrenia, Paranoid
PubMed: 20196853
DOI: 10.1186/1471-244X-10-19 -
Human Molecular Genetics Mar 2010Collagen type IV is the major structural component of the basement membrane and COL4A1 mutations cause adult small vessel disease, familial porencephaly and hereditary...
Collagen type IV is the major structural component of the basement membrane and COL4A1 mutations cause adult small vessel disease, familial porencephaly and hereditary angiopathy with nephropathy aneurysm and cramps (HANAC) syndrome. Here, we show that animals with a Col4a1 missense mutation (Col4a1(+/Raw)) display focal detachment of the endothelium from the media and age-dependent defects in vascular function including a reduced response to nor-epinephrine. Age-dependent hypersensitivity to acetylcholine is abolished by inhibition of nitric oxide synthase (NOS) activity, indicating that Col4a1 mutations affect vasorelaxation mediated by endothelium-derived nitric oxide (NO). These defects are associated with a reduction in basal NOS activity and the development of heightened NO sensitivity of the smooth muscle. The vascular function defects are physiologically relevant as they maintain in part the hypotension in mutant animals, which is primarily associated with a reduced red blood cell volume due to a reduction in red blood cell number, rather than defects in kidney function. To understand the molecular mechanism underlying these vascular defects, we examined the deposition of collagen type IV in the basement membrane, and found it to be defective. Interestingly, this mutation also leads to activation of the unfolded protein response. In summary, our results indicate that mutations in COL4A1 result in a complex vascular phenotype encompassing defects in maintenance of vascular tone, endothelial cell function and blood pressure regulation.
Topics: Animals; Animals, Newborn; Blood Vessels; Cerebral Hemorrhage; Collagen Type IV; Cyclic GMP; Endothelial Cells; Erythrocyte Volume; Homeostasis; Hypotension; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Muscle, Smooth, Vascular; Mutation; Nitric Oxide; Nitric Oxide Synthase; Unfolded Protein Response; Vasodilation
PubMed: 20056676
DOI: 10.1093/hmg/ddp584 -
Neurology Dec 2009COL4A1 mutations cause familial porencephaly, infantile hemiplegia, cerebral small vessel disease (CSVD), and hemorrhagic stroke. We recently described hereditary...
BACKGROUND
COL4A1 mutations cause familial porencephaly, infantile hemiplegia, cerebral small vessel disease (CSVD), and hemorrhagic stroke. We recently described hereditary angiopathy with nephropathy, aneurysm, and muscle cramps (HANAC) syndrome in 3 families with closely localized COL4A1 mutations. The aim of this study was to describe the cerebrovascular phenotype of HANAC.
METHODS
Detailed clinical data were collected in 14 affected subjects from the 3 families. MRI and magnetic resonance angiography (MRA) were performed in 9 of them. Skin biopsies were analyzed by electron microscopy in affected subjects in the 3 families.
RESULTS
Only 2 of 14 subjects had clinical cerebrovascular symptoms: a minor ischemic stroke at age 47 years and a small posttraumatic hemorrhage under anticoagulants at age 48 years. MRI-MRA showed cerebrovascular lesions in 8 of 9 studied subjects (mean age 39.4 years, 21-57 years), asymptomatic in 6 of them. Unique or multiple intracranial aneurysms, all on the carotid siphon, were observed in 5 patients. Seven patients had a CSVD characterized by white matter changes (7/7) affecting subcortical, periventricular, or pontine regions, dilated perivascular spaces (5/7), and lacunar infarcts (4/7). Infantile hemiplegia, major stroke, and porencephaly were not observed. Skin biopsies showed alterations of basement membranes at the dermoepidermal junction associated with expansion of extracellular matrix between smooth vascular cells in the arteriolar wall.
CONCLUSION
The cerebrovascular phenotype in hereditary angiopathy with nephropathy, aneurysm, and muscle cramps syndrome associates a cerebral small vessel disease and a large vessel disease with aneurysms of the carotid siphon. It is consistent with a lower susceptibility to hemorrhagic stroke than in familial porencephaly, suggesting an important clinical heterogeneity in the phenotypic expression of disorders related to COL4A1 mutations.
Topics: Abnormalities, Multiple; Adult; Aneurysm; Cerebrovascular Disorders; Collagen Type IV; Family Health; Female; Genetic Predisposition to Disease; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Male; Microscopy, Electron, Transmission; Middle Aged; Muscle Cramp; Mutation; Radiography; Skin; Young Adult
PubMed: 19949034
DOI: 10.1212/WNL.0b013e3181c3fd12 -
Journal of Ultrasound in Medicine :... Dec 2009The purpose of this study was to evaluate the importance of echogenic material in the fetal frontal horns.
OBJECTIVE
The purpose of this study was to evaluate the importance of echogenic material in the fetal frontal horns.
METHODS
This was a Health Insurance Portability and Accountability Act-compliant, Institutional Review Board-approved retrospective study. In part 1 of the study, prenatal sonography, prenatal magnetic resonance imaging (MRI), and birth outcomes of 17 fetuses (mean gestational age, 19 weeks; range, 15-34 weeks) with prospective echogenic material in the frontal horns were assessed. In part 2, 400 consecutive sonographic fetal surveys (mean gestational age, 19 weeks; range, 15-38 weeks) were reviewed to determine the incidence. In part 3, 2 independent reviewers assessed the appearance of the frontal horns in 40 fetuses (20 with suspected intraventricular hemorrhage from parts 1 and 2 and 20 who were interpreted to have normal findings in part 2).
RESULTS
Part 1 of the study showed that suspected hemorrhage was unilateral in 13 fetuses and bilateral in 4. Additional findings by sonography were grade 4 intraventricular hemorrhage (n = 2), ventriculomegaly (n = 2), and porencephaly (n = 1). An additional finding by MRI was porencephaly in 1 fetus. In part 2, echogenic material in the frontal horns was identified in 3 of 400 fetuses (0.8%). In part 3, hemorrhage was probably or definitely present in 11 of the 20 fetuses with abnormalities; material looked like a cyst in 6; and normal choroid was in an abnormal position in 2 and a normal position 1. Of 19 fetuses with abnormalities, 14 had a posteriorly symmetric choroid; 9 had material of different echogenicity compared with the choroid; and 17 had an expanded frontal horn. Birth outcomes were abnormal in 7, including platelet abnormalities (n = 2), hemorrhage on imaging or pathologic examination (n = 2), extraventricular hemorrhage (n = 3), and ventriculomegaly (n = 3).
CONCLUSIONS
The incidence of echogenic material in the frontal horns is less than 1%. This does not represent the normal location of the choroid plexus and may represent hemorrhage, which may resolve without sequelae or result in ventriculomegaly and porencephaly.
Topics: Cerebral Ventricles; Echoencephalography; Female; Humans; Intracranial Hemorrhages; Pregnancy; Reproducibility of Results; Sensitivity and Specificity; Ultrasonography, Prenatal
PubMed: 19933475
DOI: 10.7863/jum.2009.28.12.1629