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Circulation May 2015Collagen type IV alpha1 (COL4A1) and alpha2 (COL4A2) form heterotrimers critical for vascular basement membrane stability and function. Patients with COL4A1 or COL4A2...
BACKGROUND
Collagen type IV alpha1 (COL4A1) and alpha2 (COL4A2) form heterotrimers critical for vascular basement membrane stability and function. Patients with COL4A1 or COL4A2 mutations suffer from diverse cerebrovascular diseases, including cerebral microbleeds, porencephaly, and fatal intracerebral hemorrhage (ICH). However, the pathogenic mechanisms remain unknown, and there is a lack of effective treatment.
METHODS AND RESULTS
Using Col4a1 and Col4a2 mutant mouse models, we investigated the genetic complexity and cellular mechanisms underlying the disease. We found that Col4a1 mutations cause abnormal vascular development, which triggers small-vessel disease, recurrent hemorrhagic strokes, and age-related macroangiopathy. We showed that allelic heterogeneity, genetic context, and environmental factors such as intense exercise or anticoagulant medication modulated disease severity and contributed to phenotypic heterogeneity. We found that intracellular accumulation of mutant collagen in vascular endothelial cells and pericytes was a key triggering factor of ICH. Finally, we showed that treatment of mutant mice with a US Food and Drug Administration-approved chemical chaperone resulted in a decreased collagen intracellular accumulation and a significant reduction in ICH severity.
CONCLUSIONS
Our data are the first to show therapeutic prevention in vivo of ICH resulting from Col4a1 mutation and imply that a mechanism-based therapy promoting protein folding might also prevent ICH in patients with COL4A1 and COL4A2 mutations.
Topics: Animals; Blood Vessels; Blood-Brain Barrier; Brain; Cerebral Hemorrhage; Collagen; Collagen Type IV; Disease Models, Animal; Endothelial Cells; Female; Gene-Environment Interaction; Genetic Heterogeneity; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mutation; Neovascularization, Physiologic; Peptide Fragments; Pericytes; Phenotype; Physical Conditioning, Animal; Porencephaly; Retinal Vessels
PubMed: 25753534
DOI: 10.1161/CIRCULATIONAHA.114.013395 -
The Nigerian Postgraduate Medical... Mar 2015The aim of this study was to describe the role of computed tomography (CT) scan in the management and evaluation of children with cerebral palsy (CP) and to categorize...
AIMS AND OBJECTIVES
The aim of this study was to describe the role of computed tomography (CT) scan in the management and evaluation of children with cerebral palsy (CP) and to categorize the CT findings and then relate them to their respective aetiologies, as well as the types of CP.
MATERIALS AND METHODS
The CT findings in 32 children consisted of 16 boys and 16 girls with age range of 2-61 months who were diagnosed of CP and with detailed clinical information were analysed. The 84.4% positive CT findings were analyzed to evaluate their relationship with the clinical types, as well as the aetiological basis for the CP.
RESULTS
The spastic type found in 78.1% of the total number of children, had the highest positive findings. The yield was increased in children with birth asphyxia (46.9%) and neonatal jaundice (37.5%). The findings were those of cerebral atrophy in 46.9%, infarcts in 12.5%, hydrocephalus in 9.4% and porencephaly 6.3% of cases. Treatable lesions, such as Dandy Walker syndrome, tumour, hydrocephalus and porencephaly were identified in 25% of cases.
CONCLUSION
CT scan is no doubt efficacious in the management and evaluation of children with CP.
PubMed: 25875416
DOI: No ID Found -
Radiology Case Reports Nov 2022In children at risk of neurological damage, such as those delivered prematurely or with history of birth asphyxia, cranial ultrasonography is frequently employed....
In children at risk of neurological damage, such as those delivered prematurely or with history of birth asphyxia, cranial ultrasonography is frequently employed. Cranial ultrasonography also detects cysts, asymmetrical ventricles, periventricular white matter echogenicity, and hemorrhage, among other features. We report the case of an 8-month-old boy who was brought to the emergency department with a history of head trauma followed by seizures. Bedside cranial ultrasonography revealed multiple bilateral intracranial cysts, consistent with porencephalic cysts. Brain magnetic resonance imaging is the gold standard for identifying porencephaly and distinguishing it from other cysts. However, because of time restrictions in emergencies, cranial ultrasonography for a quick assessment in neonates and infants can be appropriate, as was the case in our encounter.
PubMed: 36111183
DOI: 10.1016/j.radcr.2022.08.042 -
Frontiers in Pediatrics 2022During sepsis and septic shock, the host's immune systems generate an overwhelming and often, detrimental, inflammatory response. Part of this response results in...
INTRODUCTION
During sepsis and septic shock, the host's immune systems generate an overwhelming and often, detrimental, inflammatory response. Part of this response results in significant alterations in blood flow and vasomotor tone regulated in part by endothelial and vascular smooth muscle cells. Here, we report on a series of 3 pediatric patients for whom vascular response was assessed by laser doppler perfusion coupled to iontophoresis over the first 2 weeks after hospitalization for septic shock to demonstrate similarities and dissimilarities in the vascular response.
CASE PRESENTATIONS
A 12-year-old male with a history of Burkitt's Lymphoma, a 21-year-old male with congenital porencephaly and epilepsy, and a 7-year-old male with no significant past medical history all were admitted to a tertiary care children's hospital with a diagnosis of septic shock requiring vasoactive infusions to maintain mean arterial blood pressure. Non-invasive laser doppler perfusion coupled with iontophoresis of either acetylcholine (endothelial-dependent response) or sodium nitroprusside (endothelial-independent response) was performed on hospital days 1, 3, 7, and 14. Variability and heterogeneity were demonstrated by the temporal assessments of the vascular response to sodium nitroprusside, but all three patients showed significant similarity in the temporal responsiveness to acetylcholine.
CONCLUSION
Assessment of baseline and temporal responsiveness to endothelial-dependent vascular reactivity may provide a predictable timeline to the resolution of pediatric septic shock.
PubMed: 35935367
DOI: 10.3389/fped.2022.939886 -
The Canadian Veterinary Journal = La... Nov 2023A 16-month-old neutered male domestic shorthair cat weighing 2.7 kg was referred for further evaluation of acute generalized muscle weakness and paraparesis after a...
A 16-month-old neutered male domestic shorthair cat weighing 2.7 kg was referred for further evaluation of acute generalized muscle weakness and paraparesis after a long-standing history of polyuria-polydipsia. The diagnosis of hypodipsic/adipsic hypernatremia relied on the key findings of absent spontaneous drinking despite hypernatremia and a hyperosmolar state (444.8 mOsm/kg, reference interval 280 to 310 mOsm/kg). Brain MRI revealed severe multifocal anatomic anomalies of the rostral calvarium and the forebrain, suggestive of encephaloclastic porencephaly. Involvement of the thalamic and hypothalamic regions could have been responsible for the cat's adipsic hypernatremia. The unique aspects of this case were the rare description of central nervous system disease leading to hypodipsia, and the history of chronic polydipsia before the acute onset of hypodipsia. Key clinical message: Multifocal abnormalities of the forebrain can present with polyuria-polydipsia syndrome, hypodipsia/adipsia, or both, depending on the stage of the disease. This likely happens when the hypothalamic and thalamic regions are affected, since they regulate antidiuretic hormone release and thirst, respectively.
Topics: Male; Cats; Animals; Hypernatremia; Polyuria; Thirst; Polydipsia; Craniocerebral Trauma; Cat Diseases
PubMed: 37915774
DOI: No ID Found -
Biology Open Aug 2019The Deciphering the Mechanisms of Developmental Disorders (DMDD) program uses a systematic and standardised approach to characterise the phenotype of embryos stemming...
The Deciphering the Mechanisms of Developmental Disorders (DMDD) program uses a systematic and standardised approach to characterise the phenotype of embryos stemming from mouse lines, which produce embryonically lethal offspring. Our study aims to provide detailed phenotype descriptions of homozygous mutants produced in DMDD and harvested at embryonic day 14.5. This shall provide new information on the role plays in organogenesis and demonstrate the capacity of the DMDD database for identifying models for researching inherited disorders. The DMDD mutants survived organogenesis and thus revealed the full spectrum of organs and tissues, the development of which depends on encoded proteins. They showed defects in the brain, cranial nerves, visual system, lungs, endocrine glands, skeleton, subepithelial tissues and mild to severe cardiovascular malformations. Together, this makes the DMDD line a useful model for identifying the spectrum of defects and for researching the mechanisms underlying autosomal dominant porencephaly 2 (OMIM # 614483), a rare human disease. Thus we demonstrate the general capacity of the DMDD approach and webpage as a valuable source for identifying mouse models for rare diseases.
PubMed: 31331924
DOI: 10.1242/bio.042895 -
Neurosurgery Dec 2020Although multilobar resections correspond to one-fifth of pediatric epilepsy surgery, there are little data on long-term seizure control.
BACKGROUND
Although multilobar resections correspond to one-fifth of pediatric epilepsy surgery, there are little data on long-term seizure control.
OBJECTIVE
To investigate the long-term seizure outcomes of children and adolescents undergoing multilobar epilepsy surgery and identify their predictors.
METHODS
In this retrospective study, we considered 69 consecutive patients that underwent multilobar epilepsy surgery at the age of 10.0 ± 5.0 yr (mean ± SD). The magnetic resonance imaging revealed a lesion in all but 2 cases. Resections were temporo-parieto(-occipital) in 30%, temporo-occipital in 41%, parieto-occipital in 16%, and fronto-(temporo)-parietal in 13% cases. Etiologies were determined as focal cortical dysplasia in 67%, perinatal or postnatal ischemic lesions in 23%, and benign tumors in 10% of cases.
RESULTS
At last follow-up of median 9 yr (range 2.8-14.8), 48% patients were seizure free; 33% were off antiepileptic drugs. 10% of patients, all with dysplastic etiology, required reoperations: 4 of 7 achieved seizure freedom. Seizure recurrence occurred mostly (80%) within the first 6 mo. Among presurgical variables, only an epileptogenic zone far from eloquent cortex independently correlated with significantly higher rates of seizure arrest in multivariate analysis. Among postsurgical variables, the absence of residual lesion and of acute postsurgical seizures was independently associated with significantly higher rates of seizure freedom.
CONCLUSION
Our study demonstrates that multilobar epilepsy surgery is effective regarding long-term seizure freedom and antiepileptic drug withdrawal in selected pediatric candidates. Epileptogenic zones-and lesions-localized distant from eloquent cortex and, thus, fully resectable predispose for seizure control. Acute postsurgical seizures are critical markers of seizure recurrence that should lead to prompt reevaluation.
Topics: Adolescent; Child; Child, Preschool; Epilepsy; Female; Humans; Male; Neurosurgical Procedures; Recurrence; Retrospective Studies; Seizures; Treatment Outcome
PubMed: 32814942
DOI: 10.1093/neuros/nyaa368 -
Journal of Veterinary Internal Medicine Mar 2017The term meningoencephalocele (MEC) describes a herniation of cerebral tissue and meninges through a defect in the cranium, whereas a meningocele (MC) is a herniation of...
BACKGROUND
The term meningoencephalocele (MEC) describes a herniation of cerebral tissue and meninges through a defect in the cranium, whereas a meningocele (MC) is a herniation of the meninges alone.
HYPOTHESIS/OBJECTIVES
To describe the clinical features, magnetic resonance imaging (MRI) characteristics, and outcomes of dogs with cranial MC and MEC.
ANIMALS
Twenty-two client-owned dogs diagnosed with cranial MC or MEC.
METHODS
Multicentric retrospective descriptive study. Clinical records of 13 institutions were reviewed. Signalment, clinical history, neurologic findings and MRI characteristics as well as treatment and outcome were recorded and evaluated.
RESULTS
Most affected dogs were presented at a young age (median, 6.5 months; range, 1 month - 8 years). The most common presenting complaints were seizures and behavioral abnormalities. Intranasal MEC was more common than parietal MC. Magnetic resonance imaging identified meningeal enhancement of the protruded tissue in 77% of the cases. Porencephaly was seen in all cases with parietal MC. Cerebrospinal fluid (CSF) analysis identified mild abnormalities in 4 of 11 cases. Surgery was not performed in any affected dog. Seventeen patients were treated medically, and seizures were adequately controlled with anti-epileptic drugs in 10 dogs. Dogs with intranasal MEC and mild neurologic signs had a fair prognosis with medical treatment.
CONCLUSION AND CLINICAL IMPORTANCE
Although uncommon, MC and MEC should be considered as a differential diagnosis in young dogs presenting with seizures or alterations in behavior. Medical treatment is a valid option with a fair prognosis when the neurologic signs are mild.
Topics: Animals; Anticonvulsants; Cerebrospinal Fluid; Dog Diseases; Dogs; Encephalocele; Female; Magnetic Resonance Imaging; Male; Meningocele; Porencephaly; Retrospective Studies; Seizures; Treatment Outcome
PubMed: 28247440
DOI: 10.1111/jvim.14638 -
Asian Journal of Psychiatry Dec 2020
Topics: Brain; Capgras Syndrome; Delusions; Humans; Porencephaly
PubMed: 32653846
DOI: 10.1016/j.ajp.2020.102289 -
Journal of Neuropathology and... Sep 2021
Topics: Adult; Collagen Type IV; Female; Humans; Intracranial Hemorrhages; Mutation; Porencephaly; Pregnancy; Ultrasonography, Prenatal
PubMed: 33846711
DOI: 10.1093/jnen/nlab026