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Ruben Kuzniecky - One of the best experts on this subject based on the ideXlab platform.
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temporal lobectomy in congenital Porencephaly associated with hippocampal sclerosis
JAMA Neurology, 2003Co-Authors: Jorge G Burneo, Edward Faught, Martina Bebin, R Morawetz, Robert C Knowlton, Roy C Martin, Ruben KuznieckyAbstract:Background Clinical and neuroimaging features of patients with epilepsy and coexisting extratemporal Porencephaly and hippocampal sclerosis have been previously described. Objective To present the clinical characteristics and surgical outcome of 6 patients with intractable epilepsy and coexisting extratemporal Porencephaly and hippocampal sclerosis. Patients and Methods Twenty-four patients with Porencephaly and epilepsy were studied. Of these, 6 had an epileptogenic focus in the temporal region. All patients underwent video electroencephalogram monitoring, magnetic resonance imaging studies, and neuropsychological evaluation. Of the subset of patients with temporal lobe epilepsy, 1 patient underwent intracranial electroencephalogram monitoring. Temporal lobe resection was performed in 5 patients. Outcomes were evaluated using the Engel classification. Results Freedom from seizures was achieved in all patients. Pathologic analysis of the resected tissue confirmed the presurgical diagnosis of mesial temporal sclerosis. Conclusion Patients with extratemporal Porencephaly and intractable seizures should be evaluated early and be considered for temporal lobectomy if clinical, magnetic resonance imaging, and electroencephalogram findings support the diagnosis of temporal lobe onset seizures.
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congenital Porencephaly mr features and relationship to hippocampal sclerosis
American Journal of Neuroradiology, 1998Co-Authors: Ruben Kuzniecky, Frank Gilliam, Edward Faught, Martina Bebin, R MorawetzAbstract:PURPOSE: We determined the frequency of amygdalar-hippocampal atrophy in patients with congenital Porencephaly-related seizure disorders to ascertain whether specific MR features of the Porencephaly correlate with amygdalar-hippocampal atrophy and epilepsy. METHODS: We studied brain MR images of 22 patients with congenital Porencephaly and measured the volume of the amygdala, the hippocampal formation, and the porencephalic cyst. We then compared imaging features with seizure symptoms. RESULTS: Porencephaly was unilateral in 20 patients and bilateral in two. Eighteen patients had cortical or subcortical cavitation and four had encephaloclastic changes (noncircumscribed parenchymal destruction associated with cystic components). The Porencephaly was located in the middle cerebral artery territory in 12 patients, in the posterior cerebral artery in four, in the internal carotid artery in two, and in multiple vessels in four. The volume of the porencephalic cyst ranged from 1% to 32% of total intracranial volume (mean, 11%). Volumetry detected atrophy of the hippocampal formation in 21 cases (11 unilateral, 10 bilateral) and atrophy of the amygdala in 12 (nine unilateral, three bilateral). No correlation was found between size or location of the Porencephaly and degree of hippocampal atrophy. Seizure symptoms correlated with mesial temporal origin but not with cyst location. CONCLUSION: Amygdalar-hippocampal atrophy often coexists with congenital Porencephaly (95%), and the atrophy may be bilateral despite unilateral cysts. Hippocampal structures should be carefully assessed in patients with Porencephaly-related seizures.
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congenital Porencephaly and hippocampal sclerosis clinical features and epileptic spectrum
Neurology, 1997Co-Authors: Ruben Kuzniecky, Frank Gilliam, Edward Faught, Martina Bebin, R MorawetzAbstract:We studied clinical features and seizure localization in 14 patients with Porencephaly and intractable seizures. Perinatal complications were present in nine patients, childhood febrile convulsions in two, congenital hemiparesis in 12, and intellectual impairment in seven. Ten patients had psychoparetic complex partial seizures (CPS), three had sensorimotor simple partial seizures, and one had generalized tonic-clonic seizures. Surface EEG showed temporal onset in nine patients (one bitemporal) and extratemporal onset in four. MRI showed Porencephaly in the distribution of the middle cerebral artery in eight patients, posterior cerebral in three, internal carotid in one, and multiple vessels in two. MR-based volumetry revealed hippocampal formation atrophy in 13 patients (eight unilateral and five bilateral) and amygdalar atrophy in 10 patients (nine unilateral and one bilateral). Hippocampal formation atrophy was concordant with CPS semiology in 10 patients (71%) and with EEG temporal localization in nine patients. Two patients had pathologic confirmation of mesial temporal sclerosis and were seizure free after temporal lobectomy. We conclude that mesial temporal sclerosis often coexists with Porencephaly and is the likely seizure focus in the presence of concordant electroclinical data. This recognition implies that effective surgical intervention can be offered to certain patients with Porencephaly-related seizure disorders. The dual pathology and association with perinatal cerebral vascular occlusion suggest a common ischemic pathogenesis.
R Morawetz - One of the best experts on this subject based on the ideXlab platform.
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temporal lobectomy in congenital Porencephaly associated with hippocampal sclerosis
JAMA Neurology, 2003Co-Authors: Jorge G Burneo, Edward Faught, Martina Bebin, R Morawetz, Robert C Knowlton, Roy C Martin, Ruben KuznieckyAbstract:Background Clinical and neuroimaging features of patients with epilepsy and coexisting extratemporal Porencephaly and hippocampal sclerosis have been previously described. Objective To present the clinical characteristics and surgical outcome of 6 patients with intractable epilepsy and coexisting extratemporal Porencephaly and hippocampal sclerosis. Patients and Methods Twenty-four patients with Porencephaly and epilepsy were studied. Of these, 6 had an epileptogenic focus in the temporal region. All patients underwent video electroencephalogram monitoring, magnetic resonance imaging studies, and neuropsychological evaluation. Of the subset of patients with temporal lobe epilepsy, 1 patient underwent intracranial electroencephalogram monitoring. Temporal lobe resection was performed in 5 patients. Outcomes were evaluated using the Engel classification. Results Freedom from seizures was achieved in all patients. Pathologic analysis of the resected tissue confirmed the presurgical diagnosis of mesial temporal sclerosis. Conclusion Patients with extratemporal Porencephaly and intractable seizures should be evaluated early and be considered for temporal lobectomy if clinical, magnetic resonance imaging, and electroencephalogram findings support the diagnosis of temporal lobe onset seizures.
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congenital Porencephaly mr features and relationship to hippocampal sclerosis
American Journal of Neuroradiology, 1998Co-Authors: Ruben Kuzniecky, Frank Gilliam, Edward Faught, Martina Bebin, R MorawetzAbstract:PURPOSE: We determined the frequency of amygdalar-hippocampal atrophy in patients with congenital Porencephaly-related seizure disorders to ascertain whether specific MR features of the Porencephaly correlate with amygdalar-hippocampal atrophy and epilepsy. METHODS: We studied brain MR images of 22 patients with congenital Porencephaly and measured the volume of the amygdala, the hippocampal formation, and the porencephalic cyst. We then compared imaging features with seizure symptoms. RESULTS: Porencephaly was unilateral in 20 patients and bilateral in two. Eighteen patients had cortical or subcortical cavitation and four had encephaloclastic changes (noncircumscribed parenchymal destruction associated with cystic components). The Porencephaly was located in the middle cerebral artery territory in 12 patients, in the posterior cerebral artery in four, in the internal carotid artery in two, and in multiple vessels in four. The volume of the porencephalic cyst ranged from 1% to 32% of total intracranial volume (mean, 11%). Volumetry detected atrophy of the hippocampal formation in 21 cases (11 unilateral, 10 bilateral) and atrophy of the amygdala in 12 (nine unilateral, three bilateral). No correlation was found between size or location of the Porencephaly and degree of hippocampal atrophy. Seizure symptoms correlated with mesial temporal origin but not with cyst location. CONCLUSION: Amygdalar-hippocampal atrophy often coexists with congenital Porencephaly (95%), and the atrophy may be bilateral despite unilateral cysts. Hippocampal structures should be carefully assessed in patients with Porencephaly-related seizures.
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congenital Porencephaly and hippocampal sclerosis clinical features and epileptic spectrum
Neurology, 1997Co-Authors: Ruben Kuzniecky, Frank Gilliam, Edward Faught, Martina Bebin, R MorawetzAbstract:We studied clinical features and seizure localization in 14 patients with Porencephaly and intractable seizures. Perinatal complications were present in nine patients, childhood febrile convulsions in two, congenital hemiparesis in 12, and intellectual impairment in seven. Ten patients had psychoparetic complex partial seizures (CPS), three had sensorimotor simple partial seizures, and one had generalized tonic-clonic seizures. Surface EEG showed temporal onset in nine patients (one bitemporal) and extratemporal onset in four. MRI showed Porencephaly in the distribution of the middle cerebral artery in eight patients, posterior cerebral in three, internal carotid in one, and multiple vessels in two. MR-based volumetry revealed hippocampal formation atrophy in 13 patients (eight unilateral and five bilateral) and amygdalar atrophy in 10 patients (nine unilateral and one bilateral). Hippocampal formation atrophy was concordant with CPS semiology in 10 patients (71%) and with EEG temporal localization in nine patients. Two patients had pathologic confirmation of mesial temporal sclerosis and were seizure free after temporal lobectomy. We conclude that mesial temporal sclerosis often coexists with Porencephaly and is the likely seizure focus in the presence of concordant electroclinical data. This recognition implies that effective surgical intervention can be offered to certain patients with Porencephaly-related seizure disorders. The dual pathology and association with perinatal cerebral vascular occlusion suggest a common ischemic pathogenesis.
Peter Heutink - One of the best experts on this subject based on the ideXlab platform.
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novel mutations in three families confirm a major role of col4a1 in hereditary Porencephaly
Journal of Medical Genetics, 2006Co-Authors: Guido J Breedveld, Maarten H Lequin, Douglas B Gould, Peter Heutink, Simon W M John, I F De Coo, W F M Arts, B A Oostra, G M S ManciniAbstract:Background: Porencephaly (cystic cavities of the brain) is caused by perinatal vascular accidents from various causes. Several familial cases have been described and autosomal dominant inheritance linked to chromosome 13q has been suggested. COL4A1 is an essential component in basal membrane stability. Mouse mutants bearing an in-frame deletion of exon 40 of Col4a1 either die from haemorrhage in the perinatal period or have Porencephaly in survivors. A report of inherited mutations in COL4A1 in two families has shown that familial Porencephaly may have the same cause in humans. Objective: To describe three novel COL4A1 mutations. Results: The three mutations occurred in three unrelated Dutch families. There were two missense mutations of glycine residues predicted to result in abnormal collagen IV assembly, and one mutation predicted to abolish the traditional COL4A1 start codon. The last mutation was also present in an asymptomatic obligate carrier with white matter abnormalities on brain magnetic resonance imaging. Conclusions: This observation confirms COL4A1 as a major locus for genetic predisposition to perinatal cerebral haemorrhage and Porencephaly and suggests variable expression of COL4A1 mutations.
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neonatal Porencephaly and adult stroke related to mutations in collagen iv a1
Annals of Neurology, 2006Co-Authors: Marjo S Van Der Knaap, Frederik Barkhof, L M E Smit, Yolande A L Pijnenburg, Sonja Zweegman, Hans W M Niessen, Saskia M Imhof, Peter HeutinkAbstract:Objective: The objective of this study was to describe leukoencephalopathy, lacunar infarcts, microbleeds and macrobleeds in the context of a collagen IV A1 mutation. Methods: We examined a family with autosomal dominant Porencephaly, in whom a defect in collagen IV A1 was detected recently. The patients underwent neurological, ophthalmological, and cardiological examinations and magnetic resonance imaging of the brain. Electron microscopy of a skin biopsy was performed. Extensive laboratory screening was performed for thrombophilia and increased bleeding tendency. Results: The Porencephaly was symptomatic in the infantile period in two patients, whereas it led to only minor neurological dysfunction in their affected mother. However, she experienced development of recurrent strokes in her 40s. In addition to the Porencephaly, all patients had a leukoencephalopathy, which was most severe in the mother. Her magnetic resonance imaging results also showed lacunar infarcts, macrobleeds and a multitude of microbleeds. No other risk factors for recurrent stroke were found. Electron microscopy showed interruptions of the basement membrane of skin capillaries and inhomogeneous thickening of the basement membrane with pools of basement membrane fragments. Interpretation: Leukoencephalopathy, ischemic infarcts, microbleeds, and macrobleeds are indicative of an underlying microangiopathy, of which the best-known causes are hypertension, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and cerebral amyloid angiopathy. Mutations in collagen IV A1, a major component of the vascular basement membrane, appear to be another risk factor.
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mutations in col4a1 cause perinatal cerebral hemorrhage and Porencephaly
Science, 2005Co-Authors: Douglas B Gould, Campbell F Phalan, Guido J Breedveld, Saskia E Van Mil, Richard S Smith, John C Schimenti, Umberto Aguglia, Marjo S Van Der Knaap, Peter Heutink, Simon W M JohnAbstract:Porencephaly is a rare neurological disease, typically manifest in infants, which is characterized by the existence of degenerative cavities in the brain. To investigate the molecular pathogenesis of Porencephaly, we studied a mouse mutant that develops Porencephaly secondary to focal disruptions of vascular basement membranes. Half of the mutant mice died with cerebral hemorrhage within a day of birth, and ∼18% of survivors had Porencephaly. We show that vascular defects are caused by a semidominant mutation in the procollagen type IV α 1 gene (Col4a1) in mice, which inhibits the secretion of mutant and normal type IV collagen. We also show that COL4A1 mutations segregate with Porencephaly in human families. Because not all mutant mice develop Porencephaly, we propose that Col4a1 mutations conspire with environmental trauma in causing the disease.
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suggestive evidence for linkage to chromosome 13qter for autosomal dominant type 1 Porencephaly
Neurology, 2004Co-Authors: Umberto Aguglia, Guido J Breedveld, Antonio Gambardella, R L Oliveri, Le E Piane, Demetrio Messina, A Quattrone, Peter HeutinkAbstract:A large three-generation family with autosomal dominant type 1 Porencephaly from southern Italy was studied. A high rate of miscarriages was observed. Of the nine affected individuals, four displayed a severe phenotype, and five had slight pyramidal signs or mild cognitive abnormalities. The MRI study disclosed unilateral porencephalic cyst, or colpocephaly. A genome-wide screen resulted in suggestive evidence for linkage to chromosome 13qter with a maximum logarithm-of-the-odds score of 3.16, from multipoint analysis, with marker D13S285.
Maarten H Lequin - One of the best experts on this subject based on the ideXlab platform.
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the expanding phenotype of col4a1 and col4a2 mutations clinical data on 13 newly identified families and a review of the literature
Genetics in Medicine, 2015Co-Authors: Marije E. C. Meuwissen, Dicky J. J. Halley, Liesbeth S. Smit, Jeske Van Harssel, Suzanne Sallevelt, Gwendolyn Woldringh, Marjo S. Van Der Knaap, Maarten H Lequin, Jan Maarten Cobben, Linda S De VriesAbstract:Two proα1(IV) chains, encoded by COL4A1, form trimers that contain, in addition, a proα2(IV) chain encoded by COL4A2 and are the major component of the basement membrane in many tissues. Since 2005, COL4A1 mutations have been known as an autosomal dominant cause of hereditary Porencephaly. COL4A1 and COL4A2 mutations have been reported with a broader spectrum of cerebrovascular, renal, ophthalmological, cardiac, and muscular abnormalities, indicated as "COL4A1 mutation-related disorders." Genetic counseling is challenging because of broad phenotypic variation and reduced penetrance. At the Erasmus University Medical Center, diagnostic DNA analysis of both COL4A1 and COL4A2 in 183 index patients was performed between 2005 and 2013. In total, 21 COL4A1 and 3 COL4A2 mutations were identified, mostly in children with Porencephaly or other patterns of parenchymal hemorrhage, with a high de novo mutation rate of 40% (10/24). The observations in 13 novel families harboring either COL4A1 or COL4A2 mutations prompted us to review the clinical spectrum. We observed recognizable phenotypic patterns and propose a screening protocol at diagnosis. Our data underscore the importance of COL4A1 and COL4A2 mutations in cerebrovascular disease, also in sporadic patients. Follow-up data on symptomatic and asymptomatic mutation carriers are needed for prognosis and appropriate surveillance.
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col4a2 mutation associated with familial Porencephaly and small vessel disease
European Journal of Human Genetics, 2012Co-Authors: Elly Verbeek, Marije E. C. Meuwissen, Paul Govaert, Daniel J Licht, Caroline J Poulton, Rachel Schot, Jeroen Dudink, Frans W. Verheijen, Maarten H Lequin, Dicky J. J. HalleyAbstract: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.
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novel mutations in three families confirm a major role of col4a1 in hereditary Porencephaly
Journal of Medical Genetics, 2006Co-Authors: Guido J Breedveld, Maarten H Lequin, Douglas B Gould, Peter Heutink, Simon W M John, I F De Coo, W F M Arts, B A Oostra, G M S ManciniAbstract:Background: Porencephaly (cystic cavities of the brain) is caused by perinatal vascular accidents from various causes. Several familial cases have been described and autosomal dominant inheritance linked to chromosome 13q has been suggested. COL4A1 is an essential component in basal membrane stability. Mouse mutants bearing an in-frame deletion of exon 40 of Col4a1 either die from haemorrhage in the perinatal period or have Porencephaly in survivors. A report of inherited mutations in COL4A1 in two families has shown that familial Porencephaly may have the same cause in humans. Objective: To describe three novel COL4A1 mutations. Results: The three mutations occurred in three unrelated Dutch families. There were two missense mutations of glycine residues predicted to result in abnormal collagen IV assembly, and one mutation predicted to abolish the traditional COL4A1 start codon. The last mutation was also present in an asymptomatic obligate carrier with white matter abnormalities on brain magnetic resonance imaging. Conclusions: This observation confirms COL4A1 as a major locus for genetic predisposition to perinatal cerebral haemorrhage and Porencephaly and suggests variable expression of COL4A1 mutations.
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hereditary Porencephaly clinical and mri findings in two dutch families
European Journal of Paediatric Neurology, 2004Co-Authors: Grazia M S Mancini, Maarten H Lequin, I F M De Coo, W F M ArtsAbstract:Familial Porencephaly is a rare disorder causing motor impairment, hemiplegia, mental retardation and epilepsy in variable degrees. Two families with Porencephaly and apparently dominant inheritance are reported. Brain MRI findings are reviewed and described in seven affected individuals. Most patients also show white matter abnormalities in the cerebral hemisphere, also contralateral to the cystic lesion. In the first family an obligate carrier was identified who did not have a cystic lesion but clear abnormalities of the white matter. Although a predisposition for thrombophilia has previously been reported, we did not observe any genetic, environmental or epigenetic predisposition for the Porencephaly. The lesions are most compatible with a deep venous thrombosis/ischemic event occurring in a late stage of pregnancy, not necessarily aggravated by perinatal asphyxia.
Dicky J. J. Halley - One of the best experts on this subject based on the ideXlab platform.
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the expanding phenotype of col4a1 and col4a2 mutations clinical data on 13 newly identified families and a review of the literature
Genetics in Medicine, 2015Co-Authors: Marije E. C. Meuwissen, Dicky J. J. Halley, Liesbeth S. Smit, Jeske Van Harssel, Suzanne Sallevelt, Gwendolyn Woldringh, Marjo S. Van Der Knaap, Maarten H Lequin, Jan Maarten Cobben, Linda S De VriesAbstract:Two proα1(IV) chains, encoded by COL4A1, form trimers that contain, in addition, a proα2(IV) chain encoded by COL4A2 and are the major component of the basement membrane in many tissues. Since 2005, COL4A1 mutations have been known as an autosomal dominant cause of hereditary Porencephaly. COL4A1 and COL4A2 mutations have been reported with a broader spectrum of cerebrovascular, renal, ophthalmological, cardiac, and muscular abnormalities, indicated as "COL4A1 mutation-related disorders." Genetic counseling is challenging because of broad phenotypic variation and reduced penetrance. At the Erasmus University Medical Center, diagnostic DNA analysis of both COL4A1 and COL4A2 in 183 index patients was performed between 2005 and 2013. In total, 21 COL4A1 and 3 COL4A2 mutations were identified, mostly in children with Porencephaly or other patterns of parenchymal hemorrhage, with a high de novo mutation rate of 40% (10/24). The observations in 13 novel families harboring either COL4A1 or COL4A2 mutations prompted us to review the clinical spectrum. We observed recognizable phenotypic patterns and propose a screening protocol at diagnosis. Our data underscore the importance of COL4A1 and COL4A2 mutations in cerebrovascular disease, also in sporadic patients. Follow-up data on symptomatic and asymptomatic mutation carriers are needed for prognosis and appropriate surveillance.
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col4a2 mutation associated with familial Porencephaly and small vessel disease
European Journal of Human Genetics, 2012Co-Authors: Elly Verbeek, Marije E. C. Meuwissen, Paul Govaert, Daniel J Licht, Caroline J Poulton, Rachel Schot, Jeroen Dudink, Frans W. Verheijen, Maarten H Lequin, Dicky J. J. HalleyAbstract: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.