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Cureus Apr 2022
PubMed: 35463569
DOI: 10.7759/cureus.x19 -
Pediatric and Developmental Pathology :... 2022Increasing number of mutations responsible for vascular lesions, leading to ischemic or hemorrhagic stroke in young adults, has been identified in the recent years. It...
BACKGROUND
Increasing number of mutations responsible for vascular lesions, leading to ischemic or hemorrhagic stroke in young adults, has been identified in the recent years. It has been demonstrated in both mice and humans, that mutations in gene promote cerebral hemorrhages. In humans, both adults and children may be affected, and the spectrum has been broadened recently to neonates and fetuses.
METHODS
We present a cohort of eight mutated fetuses in which cerebral hemorrhages were detected by ultrasound leading to elective terminations of pregnancy.
RESULTS
Our neuropathological studies demonstrated a strikingly similar pathological pattern, dominated by supra- and infratentorial multifocal hemorrhagic lesions of various abundance and age in the vicinity of enlarged small vessels having a discontinuous wall. This was constantly associated with a spectrum of supratentorial post-ischemic damages of the grey and white matters. Morphometric studies of brain vessels confirmed vascular dilation and hypervascularization in both grey and white matters and severe attenuation of the smooth-muscle actin staining in the white matter.
CONCLUSION
These observations add to the rare human neuropathological phenotype of mutations. Its recognition is mandatory to enhance the number of tested patients in the future, as well as the genetic counseling of parents.
Topics: Cerebral Hemorrhage; Collagen Type IV; Female; Humans; Mutation; Phenotype; Pregnancy; Prenatal Diagnosis
PubMed: 35382634
DOI: 10.1177/10935266221080134 -
Autopsy & Case Reports 2022
PubMed: 35350817
DOI: 10.4322/acr.2021.351 -
Journal of Toxicologic Pathology Jan 2022A female TOYO beagle dog showed porencephaly and visual organ abnormalities. At necropsy, there was a cavity filled with cerebrospinal fluid in the right cerebral...
A female TOYO beagle dog showed porencephaly and visual organ abnormalities. At necropsy, there was a cavity filled with cerebrospinal fluid in the right cerebral hemisphere and an adhesion area between the cerebral cortex and the skull, which was partially thickened. Additionally, the right optic nerve showed a slight decrease in diameter. Histopathological examination revealed increased glial fibers and collagen fibers, hemosiderin deposition, and an increased number of microglia in the adhesion area, along with a marked reduction of the cerebral parenchyma. In the right eyeball, the retina and optic nerve showed focal atrophy in the nerve fiber layer and inner granular layer to full retinal atrophy and hypoplasia of the myelinated nerve fibers, respectively. Electron microscopic examination revealed hypoplasia of the myelin sheath of nerve fibers in the right optic nerve. This is an extremely rare case of porencephaly and congenital optic nerve hypoplasia, along with independent retinal thinning.
PubMed: 35221503
DOI: 10.1293/tox.2021-0039 -
Cureus Nov 2021Pediatric convulsive seizure is common and represents a source of major concern and anxiety for the parents. Seizures can have a broad spectrum of etiologies in...
Pediatric convulsive seizure is common and represents a source of major concern and anxiety for the parents. Seizures can have a broad spectrum of etiologies in children, including metabolic, traumatic, developmental, and infectious causes. Depending on the clinical presentation, laboratory testing and neuroimaging may be indicated in the workup of the first unprovoked afebrile seizure. We present a case of a six-year-old boy who was brought to the emergency department by his mother after an episode of convulsion. She reported that he had jerky repetitive movements of all extremities that lasted around two minutes with spontaneous termination. The child did not have a febrile illness. The mother reported no history of similar episodes. Upon examination, the child appeared alert and conscious. No dysmorphic features were evident. Initial laboratory investigations were within the normal limits. The child underwent magnetic resonance imaging for the brain, which demonstrated a large well-defined extra-axial cystic lesion occupying most of the left hemisphere that is connected to the ventricular system. The lesion had no grey-matter lining and it strictly followed the cerebrospinal fluid in all sequences. Such finding represented the diagnosis of a giant left porencephalic cyst. Porencephaly is an extremely rare neurological anomaly that may present with pediatric seizures. Magnetic resonance imaging is the gold standard modality for the diagnosis of porencephaly. The case demonstrated that porencephaly can have a massive size in a patient with normal psychoneurological development.
PubMed: 34926080
DOI: 10.7759/cureus.19623 -
Frontiers in Veterinary Science 2021This case report describes the clinical signs, magnetic resonance imaging (MRI) findings and associated (histo)pathological findings in a crossbred Belgian Blue calf...
This case report describes the clinical signs, magnetic resonance imaging (MRI) findings and associated (histo)pathological findings in a crossbred Belgian Blue calf with congenital complex brain anomaly. The calf was presented with non-progressive signs (including cerebellar ataxia) since it was born, suggestive of a multifocal intracranial lesion. A congenital anomaly was suspected and after hematology, biochemistry, serology, and cerebrospinal fluid analysis, a magnetic resonance imaging study was performed. The following suspected abnormalities were the principal changes identified: severe hydrocephalus, porencephaly, suspected partial corpus callosum agenesis (CCA), and increased fluid signal between the folia of the cerebellum. Post-mortem examination predominately reflected the MRI findings. The origin for these malformations could not be identified and there was no evidence of a causative infectious agent. Corpus callosum abnormalities have been reported in bovids before and have been linked to bovine viral diarrhea virus (BVDV) infections, as have several other central nervous system anomalies in this species. In this case, BVDV was deemed an unlikely causative agent based on serology test results and lack of typical histopathological signs. The etiology of the congenital anomaly present in this bovine calf remains unknown.
PubMed: 34631846
DOI: 10.3389/fvets.2021.700527 -
Developmental Medicine and Child... Mar 2022This is a case series of six children with unilateral cerebral palsy and hemispheric encephaloclastic lesions who were evaluated for epilepsy surgery. Seizure onset was...
This is a case series of six children with unilateral cerebral palsy and hemispheric encephaloclastic lesions who were evaluated for epilepsy surgery. Seizure onset was in the neonatal period in three children, at 17 months in two, and at 5 years in one. Their ictal and interictal electroencephalogram (EEG) abnormalities showed paradoxical lateralization to the incorrect/'normal' hemisphere or showed bilateral abnormalities. After cautious discussion regarding the discordant electroclinical profile and implications for outcome, they proceeded to a functional hemispherectomy (between ages 4-11y) with good outcomes (at 1-10y follow-up). Their clinical details, EEG findings, electrocorticography, neuroimaging, and histology are reported. Possible surgical candidacy should be evaluated early in children with refractory epilepsy, even those with complex profiles and discordant data from the different investigations. Contralateral or bilateral EEG abnormalities should not preclude consideration of hemispherectomy in children with refractory epilepsy, hemiparesis, and uniclastic lesions.
Topics: Cerebral Palsy; Child; Child, Preschool; Drug Resistant Epilepsy; Electroencephalography; Female; Follow-Up Studies; Hemispherectomy; Humans; Male; Outcome Assessment, Health Care; Paresis; Porencephaly
PubMed: 34495552
DOI: 10.1111/dmcn.15047 -
Disease Models & Mechanisms Apr 2021Collagen type IV alpha 1 and alpha 2 (COL4A1 and COL4A2) are major components of almost all basement membranes. COL4A1 and COL4A2 mutations cause a multisystem disorder...
Collagen type IV alpha 1 and alpha 2 (COL4A1 and COL4A2) are major components of almost all basement membranes. COL4A1 and COL4A2 mutations cause a multisystem disorder that can affect any organ but typically involves the cerebral vasculature, eyes, kidneys and skeletal muscles. In recent years, patient advocacy and family support groups have united under the name of Gould syndrome. The manifestations of Gould syndrome are highly variable, and animal studies suggest that allelic heterogeneity and genetic context contribute to the clinical variability. We previously characterized a mouse model of Gould syndrome caused by a Col4a1 mutation in which the severities of ocular anterior segment dysgenesis (ASD), myopathy and intracerebral hemorrhage (ICH) were dependent on genetic background. Here, we performed a genetic modifier screen to provide insight into the mechanisms contributing to Gould syndrome pathogenesis and identified a single locus [modifier of Gould syndrome 1 (MoGS1)] on Chromosome 1 that suppressed ASD. A separate screen showed that the same locus ameliorated myopathy. Interestingly, MoGS1 had no effect on ICH, suggesting that this phenotype could be mechanistically distinct. We refined the MoGS1 locus to a 4.3 Mb interval containing 18 protein-coding genes, including Fn1, which encodes the extracellular matrix component fibronectin 1. Molecular analysis showed that the MoGS1 locus increased Fn1 expression, raising the possibility that suppression is achieved through a compensatory extracellular mechanism. Furthermore, we found evidence of increased integrin-linked kinase levels and focal adhesion kinase phosphorylation in Col4a1 mutant mice that is partially restored by the MoGS1 locus, implicating the involvement of integrin signaling. Taken together, our results suggest that tissue-specific mechanistic heterogeneity contributes to the variable expressivity of Gould syndrome and that perturbations in integrin signaling may play a role in ocular and muscular manifestations.
Topics: Abnormalities, Multiple; Animals; Cerebral Hemorrhage; Chromosome Mapping; Chromosomes, Mammalian; Collagen Type IV; Eye Abnormalities; Fibronectins; Genes, Modifier; Genes, Suppressor; Genetic Loci; Integrins; Mice, Mutant Strains; Muscular Diseases; Porencephaly; Signal Transduction; Syndrome; Mice
PubMed: 34424299
DOI: 10.1242/dmm.048231 -
Brain & Development Nov 2021The collagen type IV alpha 1 chain (COL4A1) gene on 13q34 encodes one chain of collagen. COL4A1 mutations have been identified as the cause of a group of multisystemic...
BACKGROUND
The collagen type IV alpha 1 chain (COL4A1) gene on 13q34 encodes one chain of collagen. COL4A1 mutations have been identified as the cause of a group of multisystemic conditions in humans, including the brain, eyes, kidneys, muscles, and other organs at any age. Brain imaging shows a wide spectrum of abnormalities, including porencephaly, schizencephaly, polymicrogyria focal cortical dysplasia, periventricular leukoencephalopathy, ventricular dysmorphisms, and multiple brain calcifications. However, there are no reports in the literature showing progressive radiological findings in consecutive follow-up scans. Herein, we report three cases of COL4A1 mutations with porencephaly from gestation to five years of age or longer, and describe their clinical and brain imaging findings.
CASE REPORTS
We retrospectively reviewed the clinical symptoms and radiological findings, including brain magnetic resonance imaging (MRI) and computed tomography (CT), in three female patients with COL4A1 mutations. Their mutations were c.4843G>A (p.Glu1615Lys), c.1835G>A (p.Gly612Asp), and c.3556+1G>T respectively. All the three cases represented porencephaly in the fetal period; severe hemolytic anemia in the neonatal period; and drug-resistant epilepsy, global developmental delay, and spastic quadriplegia in their childhood.
RESULTS
Brain MRI and CT showed progressive white matter atrophy from gestation to five-year follow-up or later. Minor cerebral hemorrhage without symptoms occasionally occurred in one patient. Despite brain changes, the clinical picture was stable during early childhood.
CONCLUSIONS
COL4A1 mutations may cause progressive cerebral atrophy beyond early childhood.
Topics: Child; Collagen Type IV; Developmental Disabilities; Drug Resistant Epilepsy; Female; Humans; Mutation; Quadriplegia
PubMed: 34281745
DOI: 10.1016/j.braindev.2021.06.008 -
Journal of Surgical Case Reports Jun 2021Surgical treatment is challenging in pediatric patients with left ventricular outflow tract (LVOT) stenosis (LVOTS). We herein present the case of a 2-year-old male...
Surgical treatment is challenging in pediatric patients with left ventricular outflow tract (LVOT) stenosis (LVOTS). We herein present the case of a 2-year-old male patient with porencephaly who was diagnosed with LVOTS accompanied by moderate mitral valve regurgitation (MR) with systolic anterior motion (SAM). Edge-to-edge mitral valve reconstruction and myectomy of the abnormal cardiac muscle were performed, with an uneventful postoperative course. LVOT myectomy and edge-to-edge mitral valve repair may be considered as a safe and acceptable approach with good clinical outcomes in pediatric patients with LVOTS accompanied by MR with SAM.
PubMed: 34194724
DOI: 10.1093/jscr/rjab240