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BMC Veterinary Research Dec 2012Seizures are a common problem in small animal neurology and it may be related to underlying diseases. Porencephaly is an extremely rare disorder, and in Veterinary...
BACKGROUND
Seizures are a common problem in small animal neurology and it may be related to underlying diseases. Porencephaly is an extremely rare disorder, and in Veterinary Medicine it affects more often ruminants, with only few reports in dogs.
CASE PRESENTATION
A one-year-old intact male Shih-Tzu dog was referred to Veterinary University Hospital with history of abnormal gait and generalized tonic-clonic seizures. Signs included hypermetria, abnormal nystagmus and increased myotatic reflexes. At necropsy, during the brain analysis, a cleft was observed in the left parietal and occipital lobes, creating a communication between the subarachnoid space and the left lateral ventricle, consistent with porencephaly; and also a focal atrophy of the caudal paravermal and vermal portions of the cerebellum. Furthermore, the histological examination showed cortical and cerebellar neuronal dysplasia.
CONCLUSIONS
Reports of seizures due to porencephaly are rare in dogs. In this case, the dog presented a group of brain abnormalities which per se or in assemblage could result in seizure manifestation.
Topics: Animals; Brain Diseases; Dog Diseases; Dogs; Male; Malformations of Cortical Development; Seizures
PubMed: 23269021
DOI: 10.1186/1746-6148-8-246 -
Developmental Medicine and Child... Feb 2013To investigate the association between magnetic resonance imaging (MRI) patterns and motor function, epileptic episodes, and IQ or developmental quotient in patients...
AIM
To investigate the association between magnetic resonance imaging (MRI) patterns and motor function, epileptic episodes, and IQ or developmental quotient in patients born at term with spastic diplegia.
METHOD
Eighty-six patients born at term with cerebral palsy (CP) and spastic diplegia (54 males, 32 females; median age 20 y, range 7-42 y) among 829 patients with CP underwent brain MRI between 1990 and 2008. The MRI and clinical findings were analysed retrospectively. Intellectual disability was classified according to the Enjoji developmental test or the Wechsler Intelligence Scale for Children (3rd edition).
RESULTS
The median ages at diagnosis of CP, assignment of Gross Motor Function Classification System (GMFCS) level, cognitive assessment, and MRI were 2 years (range 5 mo-8 y), 6 years (2 y 8 mo-19 y), 6 years (1 y 4 mo-19 y), and 7 years (10 mo-30 y) respectively. MRI included normal findings (41.9%), periventricular leukomalacia, hypomyelination, and porencephaly/periventricular venous infarction. The frequency of patients in GMFCS levels III to V and intellectual disability did not differ between those with normal and abnormal MRI findings. Patients with normal MRI findings had significantly fewer epileptic episodes than those with abnormal ones (p=0.001).
INTERPRETATION
Varied MRI findings, as well as the presence of severe motor dysfunction and intellectual disability (despite normal MRI), suggest that patients born at term with spastic diplegia had heterogeneous and unidentified pathophysiology.
Topics: Adolescent; Adult; Brain; Cerebral Palsy; Child; Epilepsy; Female; Humans; Intelligence; Magnetic Resonance Imaging; Male; Motor Skills; Nerve Fibers, Myelinated
PubMed: 23121133
DOI: 10.1111/dmcn.12013 -
Human Molecular Genetics Jan 2013Mutations in COL4A1 have been identified in families with hereditary small vessel disease of the brain presumably due to a dominant-negative mechanism. Here, we report...
Mutations in COL4A1 have been identified in families with hereditary small vessel disease of the brain presumably due to a dominant-negative mechanism. Here, we report on two novel mutations in COL4A1 in two families with porencephaly, intracerebral hemorrhage and severe white matter disease caused by haploinsufficiency. Two families with various clinical presentations of cerebral microangiopathy and autosomal dominant inheritance were examined. Clinical, neuroradiological and genetic investigations were performed. Electron microscopy of the skin was also performed. In one of the families, sequence analysis revealed a one base deletion, c.2085del, leading to a frameshift and a premature stopcodon, p.(Gly696fs). In the other family, a splice site mutation was identified, c.2194-1G>A, which most likely leads to skipping of an exon with a frameshift and premature termination as a result. In fibroblasts of affected individuals from both the families, nonsense-mediated decay (NMD) of the mutant COL4A1 messenger RNAs (mRNAs) and a clear reduction of COL4A1 protein expression were demonstrated, indicating haploinsufficiency of COL4A1. Moreover, thickening of the capillary basement membrane in the skin was documented, similar to reports in patients with COL4A1 missense mutations. These findings suggest haploinsufficiency, a different mechanism from the commonly assumed dominant-negative effect, for COL4A1 mutations as a cause of (antenatal) intracerebral hemorrhage and white matter disease.
Topics: Adult; Aged; Base Sequence; Basement Membrane; Brain; Cerebral Small Vessel Diseases; Collagen Type IV; Female; Fibroblasts; Haploinsufficiency; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Mutation; Pedigree; Young Adult
PubMed: 23065703
DOI: 10.1093/hmg/dds436 -
Iranian Red Crescent Medical Journal Jul 2012
PubMed: 22997566
DOI: No ID Found -
Journal of Korean Neurosurgical Society Apr 2012A 20-month-old boy presented with a intraparenchymal mass in the right frontoparietal area manifesting as complex partial seizure, secondary generalization and left...
A 20-month-old boy presented with a intraparenchymal mass in the right frontoparietal area manifesting as complex partial seizure, secondary generalization and left hemiparesis. Magnetic resonance images (MRI) of the brain showed inhomogeneously enhancing mass in the right frontoparietal area which has irregular margin and perilesional edema. Based on the radiological findings, a preoperative diagnosis was an intraaxial tumor, such as pilocytic astrocytoma or dysembryoplastic neuroepithelial tumor. The patient underwent a surgery including frontal craniotomy. The tumor had a partially extreme adherence to the surrounding brain tissue but it showed no dural attachment. Gross-total resection of the tumor was achieved. Postoperative follow-up computed tomography scans showed no residual tumor. The pathological findings confirmed the tumor as a WHO grade I meningioma, transitional type. Nine months after the surgery, follow-up brain MRI showed no recurrence of the tumor, porencephaly in site where the tumor was resected; the patient's symptoms had fully recovered. We report the case of a meningioma in a 20-month-old boy.
PubMed: 22737302
DOI: 10.3340/jkns.2012.51.4.219 -
Ultrasound in Obstetrics & Gynecology :... Dec 2012Prenatal development of the brain is characterized by gestational age-specific changes in the laminar structure of the brain parenchyma before 30 gestational weeks....
OBJECTIVES
Prenatal development of the brain is characterized by gestational age-specific changes in the laminar structure of the brain parenchyma before 30 gestational weeks. Cerebral lamination patterns of normal fetal brain development have been described histologically, by postmortem in-vitro magnetic resonance imaging (MRI) and by in-vivo fetal MRI. The purpose of this study was to evaluate the sonographic appearance of laminar organization of the cerebral wall in normal and abnormal brain development.
METHODS
This was a retrospective study of ultrasound findings in 92 normal fetuses and 68 fetuses with abnormal cerebral lamination patterns for gestational age, at 17-38 weeks' gestation. We investigated the visibility of the subplate zone relative to the intermediate zone and correlated characteristic sonographic findings of cerebral lamination with gestational age in order to evaluate transient structures.
RESULTS
In the normal cohort, the subplate zone-intermediate zone interface was identified as early as 17 weeks, and in all 57 fetuses examined up to 28 weeks. In all of these fetuses, the subplate zone appeared anechoic and the intermediate zone appeared homogeneously more echogenic than did the subplate zone. In the 22 fetuses between 28 and 34 weeks, there was a transition period when lamination disappeared in a variable fashion. The subplate zone-intermediate zone interface was not identified in any fetus after 34 weeks (n=13). There were three patterns of abnormal cerebral lamination: (1) no normal laminar pattern before 28 weeks (n=32), in association with severe ventriculomegaly, diffuse ischemia, microcephaly, teratogen exposure or lissencephaly; (2) focal disruption of lamination before 28 weeks (n=24), associated with hemorrhage, porencephaly, stroke, migrational abnormalities, thanatophoric dysplasia, meningomyelocele or encephalocele; (3) increased prominence and echogenicity of the intermediate zone before 28 weeks and/or persistence of a laminar pattern beyond 33 weeks (n=10), associated with Type 1 lissencephaly or CMV infection. There was a mixed focal/diffuse pattern in two fetuses. In CMV infection, the earliest indication of the infection was focal heterogeneity and increased echogenicity of the intermediate zone, which predated the development of microcephaly, ventriculomegaly and intracranial calcification.
CONCLUSIONS
The fetal subplate and intermediate zones can be demonstrated reliably on routine sonography before 28 weeks and disappear after 34 weeks. These findings represent normal gestational age-dependent transient laminar patterns of cerebral development and are consistent with histological studies. Abnormal fetal cerebral lamination patterns for gestational age are also visible on sonography, and may indicate abnormal brain development.
Topics: Brain Diseases; Cerebrum; Fetal Development; Fetus; Gestational Age; Humans; Magnetic Resonance Imaging; Retrospective Studies; Ultrasonography, Prenatal
PubMed: 22610990
DOI: 10.1002/uog.11164 -
Emerging Infectious Diseases Jun 2012
Topics: Animals; Animals, Newborn; Bunyaviridae Infections; Cattle; Cattle Diseases; Cerebellar Diseases; Cerebellum; Euthanasia, Animal; Fatal Outcome; Female; Orthobunyavirus
PubMed: 22607989
DOI: 10.3201/eid1806.120104 -
Developmental Medicine and Child... Jun 2012To describe the clinical and radiological features of four new families with a childhood presentation of COL4A1 mutation. (Review)
Review
AIM
To describe the clinical and radiological features of four new families with a childhood presentation of COL4A1 mutation.
METHOD
We retrospectively reviewed the clinical presentation. Investigations included radiological findings and COL4A1 mutation analysis of the four cases. Affected family members were identified. COL4A1 mutation analysis was performed in all index cases and, where possible, in affected family members.
RESULTS
The three male and one female index cases presented with recurrent childhood-onset stroke, infantile hemiplegia/spastic quadriplegia, and infantile spasms. Additional features such as congenital cataracts and anterior segment dysgenesis were present. Microcephaly and developmental delay/learning difficulties were present in three cases. Three cases had one or more family member affected in multiple generations, with a total of 11 such individuals identified. The clinical features showed a wide intrafamilial variation. Magnetic resonance imaging (MRI) showed bilateral white matter change in all cases, except in one mutation-positive family member. Unilateral or bilateral porencephaly was present in cases with infantile hemiplegia, and a diagnosis of clinical stroke was supported by the presence of intracerebral haemorrhage. The age at diagnosis was between 1 year and 6 years for the children with presentation in infancy and 12 months after stroke in a 14-year-old male. Three new pathogenic mutations were identified in the COL4A1 gene.
INTERPRETATION
COL4A1 mutations can present in children with infantile hemiplegia/quadriplegia, stroke or epilepsy, and a motor disorder. The presence of eye features and white matter change on MRI in childhood can help point towards the diagnosis. Once the diagnosis is made, a careful search can identify affected family members.
Topics: Adolescent; Brain; Brain Diseases; Child; Child, Preschool; Collagen Type IV; Eye Abnormalities; Family Health; Female; Hemiplegia; Humans; Infant; Magnetic Resonance Imaging; Male; Mutation; Porencephaly; Retrospective Studies
PubMed: 22574627
DOI: 10.1111/j.1469-8749.2011.04198.x -
Annals of Neurology Apr 2012Mutations in the type IV collagen alpha 1 gene (COL4A1) cause dominantly inherited cerebrovascular disease. We seek to determine the extent to which COL4A1 mutations...
OBJECTIVE
Mutations in the type IV collagen alpha 1 gene (COL4A1) cause dominantly inherited cerebrovascular disease. We seek to determine the extent to which COL4A1 mutations contribute to sporadic, nonfamilial, intracerebral hemorrhages (ICHs).
METHODS
We sequenced COL4A1 in 96 patients with sporadic ICH. The presence of putative mutations was tested in 145 ICH-free controls. The effects of rare coding variants on COL4A1 biosynthesis were compared to previously validated mutations that cause porencephaly, small vessel disease, and hereditary angiopathy, nephropathy, aneurysms, and cramps (HANAC) syndrome.
RESULTS
We identified 2 rare nonsynonymous variants in ICH patients that were not detected in controls, 2 rare nonsynonymous variants in controls that were not detected in patients, and 2 common nonsynonymous variants that were detected in patients and controls. No variant found in controls affected COL4A1 biosynthesis. Both variants (COL4A1(P352L) and COL4A1(R538G)) found only in patients changed conserved amino acids and impaired COL4A1 secretion much like mutations that cause familial cerebrovascular disease.
INTERPRETATION
This is the first assessment of the broader role for COL4A1 mutations in the etiology of ICH beyond a contribution to rare and severe familial cases and the first functional evaluation of the biosynthetic consequences of an allelic series of COL4A1 mutations that cause cerebrovascular disease. We identified 2 putative mutations in 96 patients with sporadic ICH and showed that these and other previously validated mutations inhibit secretion of COL4A1. Our data support the hypothesis that increased intracellular accumulation of COL4A1, decreased extracellular COL4A1, or both, contribute to sporadic cerebrovascular disease and ICH.
Topics: Aged; Amino Acid Sequence; Blotting, Western; Cerebral Hemorrhage; Cerebrovascular Disorders; Collagen Type IV; DNA Mutational Analysis; Female; Genetic Predisposition to Disease; Humans; Male; Molecular Sequence Data; Mutation
PubMed: 22522439
DOI: 10.1002/ana.22682 -
Journal of Toxicologic Pathology Mar 2012Porencephaly was observed in a female cynomolgus monkey (Macaca fascicularis) aged 5 years and 7 months. The cerebral hemisphere exhibited diffuse brownish excavation...
Porencephaly was observed in a female cynomolgus monkey (Macaca fascicularis) aged 5 years and 7 months. The cerebral hemisphere exhibited diffuse brownish excavation with partial defects of the full thickness of the hemispheric wall, and it constituted open channels between the lateral ventricular system and arachnoid space. In addition, the bilateral occipital lobe was slightly atrophied. Histopathologically, fibrous gliosis was spread out around the excavation area and its periphery. In the roof tissue over the cavity, small round cells were arranged in the laminae. They seemed to be neural or glial precursor cells because they were positive for Musashi 1 and negative for NeuN and GFAP. In the area of fibrous gliosis, hemosiderin or lipofuscin were deposited in the macrophages, and activated astroglias were observed extensively around the excavation area.
PubMed: 22481858
DOI: 10.1293/tox.25.45