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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 -
Internal Medicine (Tokyo, Japan) Dec 2021
Topics: Cerebral Hemorrhage; Humans; Porencephaly
PubMed: 34148964
DOI: 10.2169/internalmedicine.7446-21 -
Journal of Neurosurgery. Case Lessons May 2021Surgical treatment of intractable epilepsy caused by porencephaly can be difficult because of poorly localizing or lateralizing electroclinical findings. The authors...
BACKGROUND
Surgical treatment of intractable epilepsy caused by porencephaly can be difficult because of poorly localizing or lateralizing electroclinical findings. The authors aimed to determine whether noninvasive evaluations are sufficient in these patients.
OBSERVATIONS
Eleven patients were included in this study. The porencephalic cyst was in the left middle cerebral artery (MCA) area in 9 patients, the left posterior cerebral artery area in 1 patient, and the bilateral MCA area in 1 patient. Interictal electroencephalography (EEG) revealed multiregional, bilateral, interictal epileptiform discharges in 5 of 11 patients. In 6 of 10 patients whose seizures were recorded, the ictal EEG was nonlateralizing. Nine patients underwent ictal single-photon emission computed tomography (SPECT), which revealed lateralized hyperperfusion in 8 of 9 cases. Fluorodeoxyglucose positron emission tomography (FDG-PET) was useful for identifying the functional deficit zone. No patient had intracranial EEG. The procedure performed was hemispherotomy in 7 patients, posterior quadrant disconnection in 3 patients, and occipital disconnection in 1 patient. A favorable seizure outcome was achieved in 10 of 11 patients without the onset of new neurological deficits.
LESSONS
Ictal SPECT was useful for confirming the side of seizure origin when electroclinical findings were inconclusive. Thorough noninvasive evaluations, including FDG-PET and ictal SPECT, enabled curative surgery without intracranial EEG. Seizure and functional outcomes were favorable.
PubMed: 35854864
DOI: 10.3171/CASE21121 -
Neurology. Genetics Apr 2021We describe a third patient with brain small vessel disease 3 (BSVD3), being the first with a homozygous essential splice site variant in the gene, with a more severe...
OBJECTIVE
We describe a third patient with brain small vessel disease 3 (BSVD3), being the first with a homozygous essential splice site variant in the gene, with a more severe phenotype than the 2 children reported earlier.
METHODS
Analysis of whole exome sequencing (WES) data of the child and parents was performed. We validated the missplicing of the homozygous variant using reverse transcription PCR and Sanger sequencing of the mRNA in a lymphocyte culture.
RESULTS
The patient presented antenatally with porencephaly on ultrasound and MRI. Postnatally, he showed a severe developmental delay, refractory epilepsy, spastic quadriplegia, and a progressive hydrocephalus. WES revealed a homozygous canonical splice site variant NM_024656.3:c.625-2A>C. PCR and Sanger sequencing of the mRNA demonstrated that 2 cryptic splice sites are activated, causing a frameshift in the major transcript and in-frame deletion in a minor transcript.
CONCLUSIONS
We report a third patient with biallelic pathogenic variants in , confirming the role of this gene in autosomal recessive BSVD3.
PubMed: 33709034
DOI: 10.1212/NXG.0000000000000564 -
European Review For Medical and... Jan 2021This article aimed to describe a novel COL4A2 mutation and the phenotypic features of two family members presenting with epilepsy and cortical development malformations.
OBJECTIVE
This article aimed to describe a novel COL4A2 mutation and the phenotypic features of two family members presenting with epilepsy and cortical development malformations.
PATIENTS AND METHODS
The first patient is a 65-year-old woman with hematuria and adult-onset seizures. Brain MRI showed closed lip schizencephaly of right lateral sulcus associated with polymicrogyria of the surrounding cortex and areas of subcortical heterotopia. The second patient is a 40-year-old man, her son. He was born post-term with neonatal distress and psychomotor developmental delay with congenital left leg paresis and strabismus, as well as childhood-onset focal motor seizures. Brain MRI showed a right nucleus-capsular porencephalic cavitation with enlargement of the homolateral ventricle and a focal right occipital cortico-subcortical encephalomalacia. A small heterotopic band was also present in the frontal left subcortical region.
RESULTS
We tested both patients with a NGS panel for genetic epilepsies, which evidenced a missense mutation in COL4A2 gene (c.2972G>A, causing the aminoacidic substitution Gly991Glu).
CONCLUSIONS
The phenotypic spectrum associated with COL4A2 mutations has not been extensively described in the literature. Testing for COL4A mutations is indicated in patients with malformations of cortical development, particularly in the presence of familial conditions, even in the absence of porencephaly or early hemorrhagic strokes.
Topics: Adult; Aged; Collagen Type IV; Female; Hemangioma, Cavernous, Central Nervous System; Humans; Magnetic Resonance Imaging; Male; Malformations of Cortical Development; Mutation
PubMed: 33577044
DOI: 10.26355/eurrev_202101_24658 -
Human Genome Variation Nov 2020Genetic causes of undiagnosed hemolytic anemia in nineteen patients were analyzed by whole-exome sequencing, and novel COL4A1 variants were identified in four patients...
Genetic causes of undiagnosed hemolytic anemia in nineteen patients were analyzed by whole-exome sequencing, and novel COL4A1 variants were identified in four patients (21%). All patients were complicated with congenital malformations of the brain, such as porencephaly or schizencephaly. In these patients, hemolysis became less severe within 2 months after birth, and red cell transfusion was no longer required after 50 days, whereas chronic hemolysis continued.
PubMed: 33298904
DOI: 10.1038/s41439-020-00130-w -
American Journal of Medical Genetics.... Sep 2021Twins have an increased risk for congenital malformations and disruptions, including defects in brain morphogenesis. We analyzed data on brain imaging, zygosity, sex,...
Twins have an increased risk for congenital malformations and disruptions, including defects in brain morphogenesis. We analyzed data on brain imaging, zygosity, sex, and fetal demise in 56 proband twins and 7 less affected co-twins with abnormal brain imaging and compared them to population-based data and to a literature series. We separated our series into malformations of cortical development (MCD, N = 39), cerebellar malformations without MCD (N = 13), and brain disruptions (N = 11). The MCD group included 37/39 (95%) with polymicrogyria (PMG), 8/39 (21%) with pia-ependymal clefts (schizencephaly), and 15/39 (38%) with periventricular nodular heterotopia (PNH) including 2 with PNH but not PMG. Cerebellar malformations were found in 19 individuals including 13 with a cerebellar malformation only and another 6 with cerebellar malformation and MCD. The pattern varied from diffuse cerebellar hypoplasia to classic Dandy-Walker malformation. Brain disruptions were seen in 11 individuals with hydranencephaly, porencephaly, or white matter loss without cysts. Our series included an expected statistically significant excess of monozygotic (MZ) twin pairs (22/41 MZ, 54%) compared to population data (482/1448 MZ, 33.3%; p = .0110), and an unexpected statistically significant excess of dizygotic (DZ) twins (19/41, 46%) compared to the literature cohort (1/46 DZ, 2%; p < .0001. Recurrent association with twin-twin transfusion syndrome, intrauterine growth retardation, and other prenatal factors support disruption of vascular perfusion as the most likely unifying cause.
Topics: Adult; Brain; Diseases in Twins; Female; Humans; Infant, Newborn; Male; Pregnancy; Review Literature as Topic; Twins, Dizygotic; Twins, Monozygotic
PubMed: 33205886
DOI: 10.1002/ajmg.a.61972 -
Frontiers in Neurology 2020COL4A1 is an essential component for basal membrane stability. Exon mutations of the COL4A1 genes are responsible for a broad spectrum of cerebral, ocular, and systemic...
COL4A1 is an essential component for basal membrane stability. Exon mutations of the COL4A1 genes are responsible for a broad spectrum of cerebral, ocular, and systemic manifestations. We describe here the phenotype of a likely pathogenic gene variant, p.Gly743Val, which is responsible for a missense mutation in the COL4A1 gene exon 30 in a three generation family with severe hypermetropia and highly penetrant porencephaly in the absence of systemic manifestations. This report highlights both the broad spectrum of COL4A1 mutations and the yield of testing the COL4A1 gene in familial ophthalmological and brain disorders.
PubMed: 33013618
DOI: 10.3389/fneur.2020.00827 -
International Journal of Molecular... Sep 2020We studied 114 primitive cerebral neoplasia, that were surgically treated, and underwent radiotherapy (RT), and compared their results to those obtained by 190 patients... (Review)
Review
We studied 114 primitive cerebral neoplasia, that were surgically treated, and underwent radiotherapy (RT), and compared their results to those obtained by 190 patients diagnosed with subcortical vascular dementia (sVAD). Patients with any form of primitive cerebral neoplasia underwent whole-brain radiotherapy. All the tumor patients had regional field partial brain RT, which encompassed each tumor, with an average margin of 2.6 cm from the initial target tumor volume. We observed in our patients who have been exposed to a higher dose of RT (30-65 Gy) a cognitive and behavior decline similar to that observed in sVAD, with the frontal dysexecutive syndrome, apathy, and gait alterations, but with a more rapid onset and with an overwhelming effect. Multiple mechanisms are likely to be involved in radiation-induced cognitive impairment. The active site of RT brain damage is the white matter areas, particularly the internal capsule, basal ganglia, caudate, hippocampus, and subventricular zone. In all cases, radiation damage inside the brain mainly focuses on the cortical-subcortical frontal loops, which integrate and process the flow of information from the cortical areas, where executive functions are "elaborated" and prepared, towards the thalamus, subthalamus, and cerebellum, where they are continuously refined and executed. The active mechanisms that RT drives are similar to those observed in cerebral small vessel disease (SVD), leading to sVAD. The RT's primary targets, outside the tumor mass, are the blood-brain barrier (BBB), the small vessels, and putative mechanisms that can be taken into account are oxidative stress and neuro-inflammation, strongly associated with the alteration of NMDA receptor subunit composition.
Topics: Adult; Blood-Brain Barrier; Brain; Brain Diseases; Cerebral Cortex; Cerebral Small Vessel Diseases; Cognitive Dysfunction; Dementia, Vascular; Female; Humans; Iatrogenic Disease; Male; Middle Aged; Neuroimmunomodulation; Oxidative Stress; Porencephaly; Radiotherapy; White Matter
PubMed: 32899565
DOI: 10.3390/ijms21186506 -
Medicine Jul 2020Foetal alcohol spectrum disorder (FASD) is a complex malformative disease caused by the teratogenic effect of alcohol consumed during pregnancy. Mothers are frequently...
INTRODUCTION
Foetal alcohol spectrum disorder (FASD) is a complex malformative disease caused by the teratogenic effect of alcohol consumed during pregnancy. Mothers are frequently reluctant to admit alcohol consumption during pregnancy. During infancy and particularly during neonatal period, differential diagnosis is difficult.
PATIENT CONCERNS
This case is represented by an Italian neonate boy small for gestational age, born by caesarean section at a gestational age of 37 weeks + 6 days by neglect and single-parent pregnancy. On physical examination, he presented particular facial features: microcephaly, epicanthal folds, flat midface, low nasal bridge, indistinct philtrum, and thin upper lip; moreover, examination revealed a macro-penis and recurvation without evidence of glans.
DIAGNOSIS
Echocardiogram showed an inter-ventricular defect of medium-muscular type and brain magnetic resonance imaging showed asymmetry of the cerebral hemispheres with hypoplasia of the left cerebral hemisphere, dilatation of the left ventricle, cerebrospinal fluid cavity, and porencephaly.
INTERVENTIONS
We investigated the ethylglucuronide (EtG) concentration in the neonate's hair by liquid chromatography-tandem mass spectrometry and we detected EtG in the infant's hair (normal value, 30 pg/mg), demonstrating prenatal alcohol exposure.
OUTCOMES
In this neonate, EtG measure in hairs permitted the diagnosis of FASD, so allowing to exclude genetic diseases associated with similar clinical findings. After this result the mother admitted that she drunk alcohol during pregnancy (she declared 3 glasses of wine every day). At the age of 6 months, the child showed a moderate neurodevelopmental delay.
CONCLUSION
This case shows that FAD should be considered in neonates with rare neurological diseases as porencephaly. In neonates and infants born to a mother who did not report alcohol use, EtG measure in hairs can significantly improve diagnosis of FASD, so allowing to exclude genetic diseases associated with similar clinical findings.
Topics: Female; Fetal Alcohol Spectrum Disorders; Glucuronates; Hair; Humans; Infant, Newborn; Italy; Male; Porencephaly; Pregnancy
PubMed: 32756128
DOI: 10.1097/MD.0000000000021384