117 results on '"*CEREBRAL cortex abnormalities"'
Search Results
2. The genetic landscape of polymicrogyria.
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James, Jesmy, Iype, Mary, Surendran, Mithran, Anitha, Ayyappan, and Thomas, Sanjeev
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GENETIC mutation , *22Q11 deletion syndrome , *ANEUPLOIDY , *GENETIC testing , *NEURAL development , *CHROMOSOME abnormalities , *CEREBRAL cortex abnormalities - Abstract
Polymicrogyria (PMG) is a relatively common complex malformation with cortical development, characterized by an exorbitant number of abnormally tiny gyri separated by shallow sulci. It is a neuronal migration disorder. Familial cases of PMG and the manifestation of PMG in patients with chromosomal aberrations and mutations indicate their important role of genetics in this disorder. The highly stereotyped and well-conserved nature of the cortical folding pattern in humans is suggestive of the genetic regulation of the process. The chromosomal abnormalities observed in PMG include deletions, duplications, chromosomal rearrangements, and aneuploidies. Two of the most common deletions in PMG are 22q11.2 deletion and 1p36 deletion. Further, mutations in several genes such as GPR56, TUBB2B, SRPX2, PAX6, EOMES, WDR62, TUBA8, KIAA1279, and COL18A1 are known to be associated with PMG. Intriguingly, these genes are responsible only for a small number of cases of PMG. The protein products of these genes are implicated in diverse molecular and cellular functions. Taken together, PMG could be the result of the disruption of several biological pathways. Different modes of Mendelian inheritance and non-Mendelian inheritance are seen in PMG. We have suggested a gene panel that can be used for the detection of malformations of cortical development. [ABSTRACT FROM AUTHOR]
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- 2022
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3. PIK3CA-related overgrowth with an uncommon phenotype: case report.
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Rotunno, Roberta, Diociaiuti, Andrea, Pisaneschi, Elisa, Carnevale, Claudia, Dentici, Marialisa, and El Hachem, May
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DNA analysis , *MOSAICISM , *BIOPSY , *MOLECULAR diagnosis , *PHOSPHOTRANSFERASES , *CAPILLARIES , *MULTIPLE human abnormalities , *NEURAL development , *BLOOD-vessel abnormalities , *CEREBRAL cortex abnormalities , *BLOOD testing , *PHENOTYPES , *CHILDREN - Abstract
Background: Megalencephaly-capillary malformation syndrome is a rare multiple-malformation syndrome secondary to somatic activating mutations in the PI3K-AKT-MTOR pathway. This is included in a heterogeneous group of disorders, now defined "PIK3CA-related overgrowth spectrum". Case presentation: We report a 22-months-old female presenting an uncommon phenotype associated with a genetic mosaicism in the PIK3CA gene, detected on DNA extracted from blood peripheral and tissue biopsy. Conclusions: NGS is the preferred method for molecular diagnosis of PROS on affected skin and overgrown tissues as primary samples. The wide phenotypic variability is based on the distribution of mosaicism, in fact the same mutation can cause different PIK3CA related disorders. Continuous understanding of the clinical spectrum and of molecular basis of PROS and their overlap will lead to improve diagnosis, management and new treatment strategies. [ABSTRACT FROM AUTHOR]
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- 2022
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4. Profiling PI3K-AKT-MTOR variants in focal brain malformations reveals new insights for diagnostic care.
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Pirozzi, Filomena, Berkseth, Matthew, Shear, Rylee, Gonzalez, Lorenzo, Timms, Andrew E, Sulc, Josef, Pao, Emily, Oyama, Nora, Forzano, Francesca, Conti, Valerio, Guerrini, Renzo, Doherty, Emily S, Saitta, Sulagna C, Lockwood, Christina M, Pritchard, Colin C, Dobyns, William B, Novotny, Edward, Wright, Jason N N, Saneto, Russell P, and Friedman, Seth
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BRAIN , *GENETIC mutation , *EPILEPSY , *PHOSPHOTRANSFERASES , *NEURAL development , *TRANSFERASES , *RESEARCH funding , *CEREBRAL cortex abnormalities , *PEPTIDES , *METABOLISM - Abstract
Focal malformations of cortical development including focal cortical dysplasia, hemimegalencephaly and megalencephaly, are a spectrum of neurodevelopmental disorders associated with brain overgrowth, cellular and architectural dysplasia, intractable epilepsy, autism and intellectual disability. Importantly, focal cortical dysplasia is the most common cause of focal intractable paediatric epilepsy. Gain and loss of function variants in the PI3K-AKT-MTOR pathway have been identified in this spectrum, with variable levels of mosaicism and tissue distribution. In this study, we performed deep molecular profiling of common PI3K-AKT-MTOR pathway variants in surgically resected tissues using droplet digital polymerase chain reaction (ddPCR), combined with analysis of key phenotype data. A total of 159 samples, including 124 brain tissue samples, were collected from 58 children with focal malformations of cortical development. We designed an ultra-sensitive and highly targeted molecular diagnostic panel using ddPCR for six mutational hotspots in three PI3K-AKT-MTOR pathway genes, namely PIK3CA (p.E542K, p.E545K, p.H1047R), AKT3 (p.E17K) and MTOR (p.S2215F, p.S2215Y). We quantified the level of mosaicism across all samples and correlated genotypes with key clinical, neuroimaging and histopathological data. Pathogenic variants were identified in 17 individuals, with an overall molecular solve rate of 29.31%. Variant allele fractions ranged from 0.14 to 22.67% across all mutation-positive samples. Our data show that pathogenic MTOR variants are mostly associated with focal cortical dysplasia, whereas pathogenic PIK3CA variants are more frequent in hemimegalencephaly. Further, the presence of one of these hotspot mutations correlated with earlier onset of epilepsy. However, levels of mosaicism did not correlate with the severity of the cortical malformation by neuroimaging or histopathology. Importantly, we could not identify these mutational hotspots in other types of surgically resected epileptic lesions (e.g. polymicrogyria or mesial temporal sclerosis) suggesting that PI3K-AKT-MTOR mutations are specifically causal in the focal cortical dysplasia-hemimegalencephaly spectrum. Finally, our data suggest that ultra-sensitive molecular profiling of the most common PI3K-AKT-MTOR mutations by targeted sequencing droplet digital polymerase chain reaction is an effective molecular approach for these disorders with a good diagnostic yield when paired with neuroimaging and histopathology. [ABSTRACT FROM AUTHOR]
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- 2022
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5. Neurodevelopmental Findings and Epilepsy in Malformations of Cortical Development.
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Şah, Olcay, Türkdoğan, Dilşad, Küçük, Selda, Takış, Gülnur, Asadov, Ruslan, Öztürk, Gülten, Ünver, Olcay, and Ekinci, Gazanfer
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EMBRYO anatomy , *PATIENT aftercare , *ACADEMIC medical centers , *ELECTROENCEPHALOGRAPHY , *EPILEPSY , *NEURAL development , *ELECTROPHYSIOLOGY , *COMPARATIVE studies , *AGE factors in disease , *CEREBRAL cortex abnormalities , *SEIZURES (Medicine) , *CHILDREN - Abstract
Aim: The purpose of this study is to classify the malformations of cortical development in children according to the embryological formation, localization, and neurodevelopmental findings. Seizure/epilepsy and electrophysiological findings have also been compared. Material and Methods: Seventy-five children (age: 1 month-16.5 years; 56% male) followed with the diagnosis of malformation of cortical development, in Marmara University Pendik Research and Educational Hospital Department of Pediatric Neurology, were included in the study. Their epilepsy characteristics, electroencephalogram (EEG) findings, and prognosis were reported. Neurodevelopmental characteristics were evaluated by the Bayley Scales of Infant and Toddler Development (Bayley-III) for the ages of 0-42 months (n = 30); the Denver Developmental Screening Test-II (DDST-II) for ages 42 months-6 years (n = 11); and the Wechsler Intelligence Scales for Children (WISC-R), used for children 6 years and older (n = 34). Results: The patients were classified as 44% premigrational (14.6% microcephaly, 24% tuberous sclerosis, 2.7% focal cortical dysplasia, 1.3% hemimegalencephaly, and 1.3% diffuse cortical dysgenesis); 17.3% migrational (14.6% lissencephaly, 2.7% heterotopia); and 38.6% postmigrational (14.6% schizencephaly, 24% polymicrogyria) developmentally. According to involved area, the classification was 34.7% hemispheric/multilobar, 33.3% diffuse, and 32% focal. Seventy-five percent of the patients had a history of epilepsy, and 92% were resistant to treatment. The seizures started before the age of 12 months in diffuse malformations, and epileptic encephalopathy was more common in microcephaly with a rate of 80% and lissencephaly with a rate of 54.5% in the first EEGs. Ninety-five percent of patients had at least one level of neurodevelopmental delay detected by DDST/Bayley-III; this was more common in patients with accompanying epilepsy (P < .05). As seen more commonly in patients with diffuse pathologies and intractable frequent seizures, mental retardation was detected by WISC-R in 64.5% of patients (P < .05). Conclusion: In cases with cortical developmental malformation, epilepsy/EEG features and neurodevelopmental prognosis can be predicted depending on the developmental process and type and extent of involvement. Patients should be followed up closely with EEG. [ABSTRACT FROM AUTHOR]
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- 2021
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6. PTEN somatic mutations contribute to spectrum of cerebral overgrowth.
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Koboldt, Daniel C, Miller, Katherine E, Miller, Anthony R, Bush, Jocelyn M, McGrath, Sean, Leraas, Kristen, Crist, Erin, Fair, Summer, Schwind, Wesley, Wijeratne, Saranga, Fitch, James, Leonard, Jeffrey, Shaikhouni, Ammar, Hester, Mark E, Magrini, Vincent, Ho, Mai-Lan, Pierson, Christopher R, Wilson, Richard K, Ostendorf, Adam P, and Mardis, Elaine R
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SOMATIC mutation , *GENETIC variation , *CHILD patients , *NUCLEOTIDE sequencing , *PHENOTYPES , *CELLULAR signal transduction , *EPILEPSY , *RESEARCH , *GENETICS , *GENETIC mutation , *RESEARCH methodology , *PHOSPHATASES , *MEDICAL cooperation , *EVALUATION research , *NEURAL development , *COMPARATIVE studies , *RESEARCH funding , *CEREBRAL cortex abnormalities , *CEREBRAL cortex ,CEREBRAL cortex surgery - Abstract
Phosphatase and tensin homologue (PTEN) regulates cell growth and survival through inhibition of the mammalian target of rapamycin (MTOR) signalling pathway. Germline genetic variation of PTEN is associated with autism, macrocephaly and PTEN hamartoma tumour syndromes. The effect of developmental PTEN somatic mutations on nervous system phenotypes is not well understood, although brain somatic mosaicism of MTOR pathway genes is an emerging cause of cortical dysplasia and epilepsy in the paediatric population. Here we report two somatic variants of PTEN affecting a single patient presenting with intractable epilepsy and hemimegalencephaly that varied in clinical severity throughout the left cerebral hemisphere. High-throughput sequencing analysis of affected brain tissue identified two somatic variants in PTEN. The first variant was present in multiple cell lineages throughout the entire hemisphere and associated with mild cerebral overgrowth. The second variant was restricted to posterior brain regions and affected the opposite PTEN allele, resulting in a segmental region of more severe malformation, and the only neurons in which it was found by single-nuclei RNA-sequencing had a unique disease-related expression profile. This study reveals brain mosaicism of PTEN as a disease mechanism of hemimegalencephaly and furthermore demonstrates the varying effects of single- or bi-allelic disruption of PTEN on cortical phenotypes. [ABSTRACT FROM AUTHOR]
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- 2021
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7. Motor Organization in Schizencephaly: Outcomes of Transcranial Magnetic Stimulation and Diffusion Tensor Imaging of Motor Tract Projections Correlate with the Different Domains of Hand Function.
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Yoon, Ju-Yul, Kim, Da-Sol, Kim, Gi-Wook, Ko, Myoung-Hwan, Seo, Jeong-Hwan, Won, Yu Hui, and Park, Sung-Hee
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DELTOID muscle physiology , *HAND physiology , *ARM physiology , *GRIP strength , *TRANSCRANIAL magnetic stimulation , *MAGNETIC resonance imaging , *RETROSPECTIVE studies , *NEURAL development , *CEREBRAL cortex abnormalities , *MOTOR neurons - Abstract
Objective. Schizencephaly is a rare congenital malformation that causes motor impairment. To determine the treatment strategy, each domain of the motor functions should be appropriately evaluated. We correlated a color map of diffusion tensor imaging (DTI) and transcranial magnetic stimulation (TMS) with the hand function test (HFT) to identify the type of hand function that each test (DTI and TMS) reflects. Further, we attempted to demonstrate the motor neuron organization in schizencephaly. Method. This retrospective study was conducted on 12 patients with schizencephaly. TMS was conducted in the first dorsal interosseous (FDI), biceps (BB), and deltoid muscles of the upper extremity, and contralateral MEP (cMEP) and ipsilateral MEP (iMEP) were recorded. The HFT included the grip strength, box and block (B&B), and 9-hole peg test. The schizencephalic cleft was confirmed using magnetic resonance imaging, and the corticospinal tract (CST) was identified using the color map of DTI. The symmetry indices for the peduncle and CST at pons level were calculated as the ratios of the cross-sectional area of the less-affected side and that of the more-affected side. Result. In the more-affected hemisphere TMS, no iMEP was obtained. In the less-affected hemisphere TMS, the iMEP response was detected in 9 patients and cMEP in all patients, which was similar to the pattern observed in unilateral lesion. Paretic hand grip strength was strongly correlated with the presence of iMEP (p = 0.044). The symmetry index of the color map of DTI was significantly correlated with the B&B (p = 0.008 , R 2 = 0.416), whereas the symmetry index of the peduncle was not correlated with all HFTs. Conclusion. In patients with schizencephaly, the iMEP response rate is correlated with the hand function related to strength, while the symmetricity of the CST by the color map of DTI is correlated with the hand function associated with dexterity. Additionally, we suggest the possible motor organization pattern of schizencephaly following interhemispheric competition. [ABSTRACT FROM AUTHOR]
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- 2021
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8. Triple Pathology in Rasmussen's Encephalitis: A New Pathological Phenotype.
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Makkar, Ayush M., Komakula, Snigdha, Agarwal, Ayush, Sahu, Saumya, Suri, Vaishali, and Srivasatava, Achal K.
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ENCEPHALITIS diagnosis , *ENCEPHALITIS , *HIPPOCAMPUS (Brain) , *ELECTROENCEPHALOGRAPHY , *NEURAL development , *AGE factors in disease , *POSITRON emission tomography , *CEREBRAL cortex abnormalities , *SEIZURES (Medicine) , *BEHAVIOR modification , *DISEASE complications - Published
- 2022
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9. Involvement of Incomplete Hippocampal Inversion in Intractable Epilepsy: Evidence from Neuropsychological Studies.
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Bhoopathy, R, Arthy, B, Vignesh, S, Ruckmani, Smitha, Srinivasan, A, Bhoopathy, R M, Vignesh, S S, and Srinivasan, A V
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HIPPOCAMPUS (Brain) , *EPILEPSY , *NEURAL development , *CEREBRAL cortex abnormalities , *SEIZURES (Medicine) , *DISEASE complications - Abstract
Background: The age of onset of seizure, seizure types, frequency of seizure, structural abnormalities in the brain, and antiepileptic medication (polytherapy) causes increased incidence of anxiety and depression in intractable epilepsy patients.Aim: To compare the anxiety and depression levels in intractable epileptic patients with structural abnormalities [malformations of cortical development (MCD) and incomplete hippocampal inversion (IHI)] and without structural abnormalities.Materials and Methods: Participants were selected from (239 males and 171 females) intractable epilepsy patients. They were grouped into four groups; Group 1: 51 nonepileptic age-matched controls, Group 2: 41 intractable epilepsy patients without any brain abnormality, Group 3: 17 intractable epilepsy patients with MCD, and Group 4: 30 intractable epilepsy patients with isolated IHI. Neuropsychiatric tools used were Multiphasic Personality Questionnaire and Weschlers Adult Intelligence Scale to assess anxiety, depression, and intelligence. Groups were classified using 1.5T conventional magnetic resonance imaging and hippocampal volumetric studies. Group comparison design was used.Results: Demographic variables of intractable epilepsy, including seizure types, the frequency of seizure, the age of seizure onset, and antiepileptic drug therapies, did not show significant association between the groups using Chi-square P value. Analysis of variance showed significant anxiety and depression in epileptic patients than the control group (P < 0.01). Post hoc analysis using Tukey's B test showed significant difference in anxiety and depression scores between group value. In group 3 and 4, anxiety scores were significantly different but not depression scores.Conclusion: The present study concludes high prevalence of anxiety and depression in intractable seizure. Anxiety is observed predominantly when there is IHI along with depression. We emphasize the need to identify IHI in intractable epilepsy and assess anxiety and depression to treat them effectively. [ABSTRACT FROM AUTHOR]- Published
- 2021
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10. Endoscopic Hemispherotomy for Nonatrophic Rasmussen's Encephalopathy.
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Doddamani, Ramesh, Chandra, P, Samala, Raghu, Ramanujan, Bhargavi, Tripathi, Madhavi, Bal, C, Garg, Ajay, Gaikwad, Shailesh, Tripathi, Manjari, Doddamani, Ramesh Sharanappa, Chandra, P Sarat, and Bal, C S
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EPILEPSY surgery , *ELECTROENCEPHALOGRAPHY , *NEUROSURGERY , *MAGNETIC resonance imaging , *NEURAL development , *TREATMENT effectiveness , *CEREBRAL cortex abnormalities - Abstract
Background: Hemispheric disconnection represents a challenging and major epilepsy surgical procedure. This procedure in experienced hands offers excellent results in terms of seizure outcomes, especially for hemispheric pathologies such as Rasmussen's encephalitis, hemispheric dysplasias, hemimegalencephaly. The technique of hemispherotomy has witnessed various modifications over the years, beginning from anatomical hemispherectomy to the current era of minimally invasive functional hemispheric disconnections.Objective: This study aimed to describe the technique of performing endoscopic vertical hemispherotomy using interhemispheric corridor developed by the senior author.Materials and Methods: A 12-year-old girl with seizure onset at the age of 10 years presented with an aura of fear and nausea followed by tonic deviation of eyes to the right and blinking with speech arrest. There were tonic-clonic movements of the right-sided limbs along with ictal spitting and occasional deviation of the angle of mouth to the right. The patient had loss of awareness for the event along with postictal confusion lasting few minutes.Results: Video electroencephalography (VEEG) revealed left parietocentral and left temporal localization. Serial magnetic resonance imaging (MRI) brain over 3 years revealed progressive left hemispheric changes suggestive of Rasmussen's encephalitis. The patient underwent left-sided endoscopic hemispherotomy. At 2 years follow-up, the patient is seizure-free (ILAE [International League Against Epilepsy] Class 1).Conclusion: Endoscopic hemispherotomy using the interhemispheric approach is an elegant, minimally invasive, reproducible, safe, and efficacious technique. [ABSTRACT FROM AUTHOR]- Published
- 2021
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11. ATP1A2- and ATP1A3-associated early profound epileptic encephalopathy and polymicrogyria.
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Vetro, Annalisa, Nielsen, Hang N, Holm, Rikke, Hevner, Robert F, Parrini, Elena, Powis, Zoe, Møller, Rikke S, Bellan, Cristina, Simonati, Alessandro, Lesca, Gaétan, Helbig, Katherine L, Palmer, Elizabeth E, Mei, Davide, Ballardini, Elisa, Haeringen, Arie Van, Syrbe, Steffen, Leuzzi, Vincenzo, Cioni, Giovanni, Curry, Cynthia J, and Costain, Gregory
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EPILEPSY , *HEMIPLEGIA , *MIGRAINE aura , *CELL survival , *HYDROPS fetalis , *CEREBRAL atrophy , *CEREBELLAR ataxia , *RESEARCH , *BRAIN diseases , *GENETIC mutation , *ANIMAL experimentation , *RESEARCH methodology , *MEDICAL cooperation , *EVALUATION research , *NEURAL development , *ADENOSINE triphosphatase , *COMPARATIVE studies , *GENOTYPES , *CEREBRAL cortex abnormalities , *PHENOTYPES - Abstract
Constitutional heterozygous mutations of ATP1A2 and ATP1A3, encoding for two distinct isoforms of the Na+/K+-ATPase (NKA) alpha-subunit, have been associated with familial hemiplegic migraine (ATP1A2), alternating hemiplegia of childhood (ATP1A2/A3), rapid-onset dystonia-parkinsonism, cerebellar ataxia-areflexia-progressive optic atrophy, and relapsing encephalopathy with cerebellar ataxia (all ATP1A3). A few reports have described single individuals with heterozygous mutations of ATP1A2/A3 associated with severe childhood epilepsies. Early lethal hydrops fetalis, arthrogryposis, microcephaly, and polymicrogyria have been associated with homozygous truncating mutations in ATP1A2. We investigated the genetic causes of developmental and epileptic encephalopathies variably associated with malformations of cortical development in a large cohort and identified 22 patients with de novo or inherited heterozygous ATP1A2/A3 mutations. We characterized clinical, neuroimaging and neuropathological findings, performed in silico and in vitro assays of the mutations' effects on the NKA-pump function, and studied genotype-phenotype correlations. Twenty-two patients harboured 19 distinct heterozygous mutations of ATP1A2 (six patients, five mutations) and ATP1A3 (16 patients, 14 mutations, including a mosaic individual). Polymicrogyria occurred in 10 (45%) patients, showing a mainly bilateral perisylvian pattern. Most patients manifested early, often neonatal, onset seizures with a multifocal or migrating pattern. A distinctive, 'profound' phenotype, featuring polymicrogyria or progressive brain atrophy and epilepsy, resulted in early lethality in seven patients (32%). In silico evaluation predicted all mutations to be detrimental. We tested 14 mutations in transfected COS-1 cells and demonstrated impaired NKA-pump activity, consistent with severe loss of function. Genotype-phenotype analysis suggested a link between the most severe phenotypes and lack of COS-1 cell survival, and also revealed a wide continuum of severity distributed across mutations that variably impair NKA-pump activity. We performed neuropathological analysis of the whole brain in two individuals with polymicrogyria respectively related to a heterozygous ATP1A3 mutation and a homozygous ATP1A2 mutation and found close similarities with findings suggesting a mainly neural pathogenesis, compounded by vascular and leptomeningeal abnormalities. Combining our report with other studies, we estimate that ∼5% of mutations in ATP1A2 and 12% in ATP1A3 can be associated with the severe and novel phenotypes that we describe here. Notably, a few of these mutations were associated with more than one phenotype. These findings assign novel, 'profound' and early lethal phenotypes of developmental and epileptic encephalopathies and polymicrogyria to the phenotypic spectrum associated with heterozygous ATP1A2/A3 mutations and indicate that severely impaired NKA pump function can disrupt brain morphogenesis. [ABSTRACT FROM AUTHOR]
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- 2021
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12. A novel de novo DDX3X missense variant in a female with brachycephaly and intellectual disability: a case report.
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Moresco, Giada, Costanza, Jole, Santaniello, Carlo, Rondinone, Ornella, Grilli, Federico, Prada, Elisabetta, Orcesi, Simona, Coro, Ilaria, Pichiecchio, Anna, Marchisio, Paola, Miozzo, Monica, Fontana, Laura, and Milani, Donatella
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GENETIC mutation , *TONGUE diseases , *NEURAL development , *GENE expression , *CRANIOSYNOSTOSES , *PEOPLE with intellectual disabilities , *CEREBRAL cortex abnormalities - Abstract
Background: De novo pathogenic variants in the DDX3X gene are reported to account for 1–3% of unexplained intellectual disability (ID) in females, leading to the rare disease known as DDX3X syndrome (MRXSSB, OMIM #300958). Besides ID, these patients manifest a variable clinical presentation, which includes neurological and behavioral defects, and abnormal brain MRIs. Case presentation: We report a 10-year-old girl affected by delayed psychomotor development, delayed myelination, and polymicrogyria (PMG). We identified a novel de novo missense mutation in the DDX3X gene (c.625C > G) by whole exome sequencing (WES). The DDX3X gene encodes a DEAD-box ATP-dependent RNA-helicase broadly implicated in gene expression through regulation of mRNA metabolism. The identified mutation is located just upstream the helicase domain and is suggested to impair the protein activity, thus resulting in the altered translation of DDX3X-dependent mRNAs. The proband, presenting with the typical PMG phenotype related to the syndrome, does not show other clinical signs frequently reported in presence of missense DDX3X mutations that are associated with a most severe clinical presentation. In addition, she has brachycephaly, never described in female DDX3X patients, and macroglossia, that has never been associated with the syndrome. Conclusions: This case expands the knowledge of DDX3X pathogenic variants and the associated DDX3X syndrome phenotypic spectrum. [ABSTRACT FROM AUTHOR]
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- 2021
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13. A novel TUBG1 mutation with neurodevelopmental disorder caused by malformations of cortical development.
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Shen, Ru, Zhang, Zhen, Zhuang, Yu, Yang, Xiaohong, and Duan, Lifen
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EPILEPSY risk factors , *GENETIC mutation , *SEQUENCE analysis , *EAR diseases , *DEVELOPMENTAL disabilities , *NEURAL development , *RISK assessment , *CHILD psychopathology , *CEREBRAL cortex abnormalities , *PEOPLE with intellectual disabilities , *PSYCHOMOTOR disorders , *GENETIC techniques , *RARE diseases , *DISEASE risk factors , *DISEASE complications - Abstract
Neurodevelopmental disorder caused by malformations of cortical development is a rare neurological disease. Heterozygous missense variants in the TUBG1 gene lead to malformations of human cortical development, which further result in intellectual disability, developmental retardation, and epilepsy. To the best of our knowledge, only thirteen patients and a total of nine pathogenic TUBG1 variants have been described in the published literature. This study reports the case details and genetic data analysis of a girl (aged 8 years, 9 months) with developmental delay, psychomotor regression, epilepsy, and left external ear deformity. A novel TUBG1 mutation was identified by whole-exome sequencing and Sanger sequencing, confirming that this mutation may be the cause of the neurodevelopmental disorders. This case report characterizes the phenotypic spectrum, molecular genetic findings, and functional consequences of novel pathogenic TUBG1 variants in neurodevelopmental disorders caused by cortical development malformations. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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14. Rare Cause of West syndrome secondary to Tubulinopathy due to Congenital Symmetric Circumferential Skin Creases (CSCSC) Kunze Type due to a Novel Variant in MAPRE2 Gene.
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Gowda, Vykuntaraju K., Srinivasan, Varunvenkat M., Reddy, Varsha, and Bhat, Maya
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SKIN diseases , *BRAIN , *INFANTILE spasms , *GENETIC mutation , *ELECTROENCEPHALOGRAPHY , *PREDNISOLONE , *EPILEPSY , *DEVELOPMENTAL disabilities , *MAGNETIC resonance imaging , *DIFFERENTIAL diagnosis , *NEURAL development , *GENOTYPES , *CEREBRAL cortex abnormalities , *SEIZURES (Medicine) , *RARE diseases , *PHENOTYPES - Published
- 2022
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15. Motor function in children with congenital Zika syndrome.
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Melo, Adriana, Gama, Gabriela L, Da Silva Júnior, Renan A, De Assunção, Paula L, Tavares, Jousilene S, Da Silva, Mariana B, Costa, Kamila N F S, Vânia, Mell L, Evangelista, Morgana A, and De Amorim, Melania M R
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MULTIPLE regression analysis , *MOTOR ability , *MOTHER-child relationship , *BRAIN damage , *CROSS-sectional method , *MOVEMENT disorders , *NEURAL development , *RESEARCH funding , *CEREBRAL cortex abnormalities - Abstract
Aim: To evaluate gross motor function and associated factors in children with congenital Zika syndrome (CZS).Method: Fifty-nine children (30 males, 29 females) with CZS at a mean (SD) age of 14.7 (3.9), months (range 5-29mo) were evaluated using the Gross Motor Function Measure (GMFM) and classified according to the Gross Motor Function Classification System (GMFCS). Neurological damage was evaluated by neuroimaging. The mothers' sociodemographic characteristics and general data on the children were obtained from interviews with the mothers and from the children's medical records. Correlational and multiple regression analyses were performed to identify factors associated with these children's motor function.Results: In 81% of the children, motor function impairment was severe, classified as GMFCS level V. The overall GMFM score ranged from 5 to 210 (median 18; interquartile range 11), with only four children receiving scores in the D and E dimensions. The factors found to affect motor function were the presence of severe malformations of cortical development and small head circumference at birth.Interpretation: Although motor impairment may be mild in some children, it is generally severe. Severe malformations of cortical development and small head circumference at birth were factors associated with poorer motor function, reflecting the greater severity of brain damage.What This Paper Adds: Motor impairment is severe in most children with congenital Zika syndrome (CZS). Motor skills are adequate or close to adequate for age in 7% of children with CZS. Severe malformations of cortical development are associated with poor motor control. Small head circumference at birth is also associated with poor motor control. [ABSTRACT FROM AUTHOR]- Published
- 2020
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16. Speech and language in bilateral perisylvian polymicrogyria: a systematic review.
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Braden, Ruth O, Leventer, Richard J, Jansen, Anna, Scheffer, Ingrid E, and Morgan, Angela T
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MEDICAL subject headings , *META-analysis , *ORAL communication , *SPEECH disorders , *SPEECH , *SUBJECT headings , *EXPRESSIVE language , *NEURAL development , *LANGUAGE & languages , *WORD deafness , *PHENOTYPES , *SYSTEMATIC reviews , *CEREBRAL cortex abnormalities , *SEVERITY of illness index , *MULTIPLE human abnormalities , *DISEASE complications - Abstract
Aim: We aimed to systematically review the speech production, language, and oral function phenotype of bilateral perisylvian polymicrogyria (BPP), and examine the correlation between the topography of polymicrogyria and the severity of speech, language, and oral functional impairment.Method: A systematic search of MEDLINE, Embase, and PubMed databases was completed on 26th October 2017 using Medical Subject Heading terms synonymous with BPP and speech, language, or oral motor impairment. In total, 2411 papers were identified and 48 met inclusion criteria.Results: Expressive and receptive language impairment and oral structural and functional deficits are frequent in BPP. Expressive deficits are frequently more severe than receptive. Only one study used formal assessments to demonstrate the presence of speech disorder, namely dysarthria. Seven studies reported an association between diffuse BPP and more severe language impairment.Interpretation: Findings confirmed that language deficits are common in BPP, though assessment of the specific speech phenotype is limited. The paucity of high quality studies detailing the specific communication phenotype of BPP highlights the need for further investigation. Improving understanding of this phenotype will inform the development of targeted therapies and lead to better long-term outcomes.What This Paper Adds: Speech, language, and oral functional impairments are common in individuals with bilateral perisylvian polymicrogyria. Posterior polymicrogyria is associated with a less severe language impairment than anterior polymicrogyria. Deeper investigation of speech is needed to understand implicated networks in this malformation. [ABSTRACT FROM AUTHOR]- Published
- 2019
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17. Further refinement of COL4A1 and COL4A2 related cortical malformations.
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Cavallin, Mara, Mine, Manuele, Philbert, Marion, Boddaert, Nathalie, Lepage, Jean Marie, Coste, Thibault, Lopez-Gonzalez, Vanessa, Sanchez-Soler, Maria Jose, Ballesta-Martínez, Maria Juliana, Remerand, Ganaëlle, Pasquier, Laurent, Guët, Agnès, Chelly, Jamel, Lascelles, Karine, Prieto-Morin, Carol, Kossorotoff, Manoelle, Tournier Lasserve, Elisabeth, and Bahi-Buisson, Nadia
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CEREBRAL cortex abnormalities , *HEMOLYTIC anemia , *MUSCLE diseases , *CREATINE kinase , *BRAIN abnormalities - Abstract
Abstract Mutations in COL4A1 have been reported in schizencephaly and porencephaly combined with microbleeds or calcifications, often associated with ocular and renal abnormalities, myopathy, elevated creatine kinase levels and haemolytic anaemia. In this study, we aimed to clarify the phenotypic spectrum of COL4A1/A2 mutations in the context of cortical malformations that include schizencephaly, polymicrogyria and/or heterotopia. Methods We screened for COL4A1/A2 mutations in 9 patients with schizencephaly and/or polymicrogyria suspected to be caused by vascular disruption and leading to a cerebral haemorrhagic ischaemic event. These included 6 cases with asymmetrical or unilateral schizencephaly and/or polymicrogyria and 3 cases with bilateral schizencephaly. Results One de novo missense COL4A1 mutation (c.3715 G > A, p.(Gly1239Arg)) and two COL4A2 mutations were found, respectively in one familial case (c.4129G > A, p.(Gly1377Arg)) and one sporadic patient (c.1776+1G > A). In three other cases, COL4A1 variants of unknown significance were identified. None of our patients demonstrated neuromuscular or hematological anomalies. Brain malformations included a combination of schizencephaly, mainly asymmetrical, with porencephaly or ventriculomegaly (3/3 mutated patients). We did not observe microbleeds or microcalcifications in any of our cases, hence we do not believe that they represent a distinctive feature of COL4A1/A2 mutations. Conclusions Our study further emphasizes the need to search for both COL4A1 and COL4A2 mutations in children presenting with uni- or bilateral polymicrogyria with schizencephaly, even in the absence of intracranial microbleeds, calcification or associated systemic features. [ABSTRACT FROM AUTHOR]
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- 2018
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18. Mutations in TBR1 gene leads to cortical malformations and intellectual disability.
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Vegas, Nancy, Cavallin, Mara, Kleefstra, Tjitske, de Boer, Lonneke, Philbert, Marion, Maillard, Camille, Boddaert, Nathalie, Munnich, Arnold, Hubert, Laurence, Bery, Amandine, Besmond, Claude, and Bahi-Buisson, Nadia
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CEREBRAL cortex abnormalities , *NEURODEGENERATION , *NEURODEVELOPMENTAL treatment , *AMINO acids , *AUTISM spectrum disorders - Abstract
Abstract The advent of next generation sequencing has improved gene discovery in neurodevelopmental disorders. A greater understanding of the genetic basis of these disorders has expanded the spectrum of pathogenic genes, thus enhancing diagnosis and therapeutic management. Genetic overlap between distinct neurodevelopmental disorders has also been revealed, which can make determining a strict genotype-phenotype correlation more difficult. Intellectual disability and cortical malformations are two neurodevelopmental disorders particularly confronted by this difficulty. Indeed, for a given pathogenic gene, intellectual disability can be associated, or not, with cortical malformations. Here, we report for the first time, two individuals with the same de novo mutation in TBR1, leading to a frameshift starting at codon Thr532, and resulting in a premature stop codon 143 amino acids downstream (c.1588_1594dup, p.(Thr532Argfs*144)). These individuals presented with a developmental encephalopathy characterized by frontal pachygyria and severe intellectual disability. Remarkably, 11 TBR1 gene mutations were previously reported in intellectual disability and autism spectrum disorders. Our study supports the observation that TBR1- related disorders range from intellectual disability to frontal pachygyria. We also highlight the need for first-line, good quality neuroimaging for patients with intellectual disability. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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19. Second-hit mosaic mutation in mTORC1 repressor DEPDC5 causes focal cortical dysplasia-associated epilepsy.
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Ribierre, Théo, Deleuze, Charlotte, Bacq, Alexandre, Baldassari, Sara, Marsan, Elise, Chipaux, Mathilde, Muraca, Giuseppe, Roussel, Delphine, Navarro, Vincent, Leguern, Eric, Miles, Richard, and Baulac, Stéphanie
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GENETICS of epilepsy , *DYSPLASIA , *GENETIC mutation , *MTOR protein , *GENETIC repressors , *PROTEIN metabolism , *PROTEINS , *RESEARCH , *FOCAL cortical dysplasia , *NEURONS , *EPILEPSY , *ANIMAL experimentation , *RESEARCH methodology , *EVALUATION research , *NEURAL development , *GENE expression , *COMPARATIVE studies , *RESEARCH funding , *CEREBRAL cortex abnormalities , *MICE , *SPINE , *METABOLISM - Abstract
DEP domain-containing 5 protein (DEPDC5) is a repressor of the recently recognized amino acid-sensing branch of the mTORC1 pathway. So far, its function in the brain remains largely unknown. Germline loss-of-function mutations in DEPDC5 have emerged as a major cause of familial refractory focal epilepsies, with case reports of sudden unexpected death in epilepsy (SUDEP). Remarkably, a fraction of patients also develop focal cortical dysplasia (FCD), a neurodevelopmental cortical malformation. We therefore hypothesized that a somatic second-hit mutation arising during brain development may support the focal nature of the dysplasia. Here, using postoperative human tissue, we provide the proof of concept that a biallelic 2-hit - brain somatic and germline - mutational mechanism in DEPDC5 causes focal epilepsy with FCD. We discovered a mutation gradient with a higher rate of mosaicism in the seizure-onset zone than in the surrounding epileptogenic zone. Furthermore, we demonstrate the causality of a Depdc5 brain mosaic inactivation using CRISPR-Cas9 editing and in utero electroporation in a mouse model recapitulating focal epilepsy with FCD and SUDEP-like events. We further unveil a key role of Depdc5 in shaping dendrite and spine morphology of excitatory neurons. This study reveals promising therapeutic avenues for treating drug-resistant focal epilepsies with mTORC1-targeting molecules. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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20. Modelling of the Current Density Distributions during Cortical Electric Stimulation for Neuropathic Pain Treatment.
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Fiocchi, S., Chiaramello, E., Ravazzani, P., and Parazzini, M.
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TREATMENT of peripheral neuropathy , *ELECTRIC stimulation , *NEURAL stimulation , *MEDICAL protocols , *CEREBRAL cortex abnormalities - Abstract
In the last two decades, motor cortex stimulation has been recognized as a valuable alternative to pharmacological therapy for the treatment of neuropathic pain. Although this technique started to be used in clinical studies, the debate about the optimal settings that enhance its effectiveness without inducing tissue damage is still open. To this purpose, computational approaches applied to realistic human models aimed to assess the current density distribution within the cortex can be a powerful tool to provide a basic understanding of that technique and could help the design of clinical experimental protocols. This study aims to evaluate, by computational techniques, the current density distributions induced in the brain by a realistic electrode array for cortical stimulation. The simulation outcomes, summarized by specific metrics quantifying the efficacy of the stimulation (i.e., the effective volume and the effective depth of penetration) over two cortical targets, were evaluated by varying the interelectrode distance, the stimulus characteristics (amplitude and frequency), and the anatomical human model. The results suggest that all these parameters somehow affect the current density distributions and have to be therefore taken into account during the planning of effective electrical cortical stimulation strategies. In particular, our calculations show that (1) the most effective interelectrode distance equals 2 cm; (2) increasing voltage amplitudes increases the effective volume; (3) increasing frequencies allow enlarging the effective volume; and (4) the effective depth of penetration is strictly linked to both the anatomy of the subject and the electrode placement. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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21. De novo mutations in GRIN1 cause extensive bilateral polymicrogyria.
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Fry, Andrew E., Fawcett, Katherine A., Zelnik, Nathanel, Hongjie Yuan, Thompson, Belinda A. N., Shemer-Meiri, Lilach, Cushion, Thomas D., Mugalaasi, Hood, Sims, David, Stoodley, Neil, Seo-Kyung Chung, Rees, Mark I., Patel, Chirag V., Brueton, Louise A., Layet, Valérie, Giuliano, Fabienne, Kerr, Michael P., Banne, Ehud, Meiner, Vardiella, and Lerman-Sagie, Tally
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MISSENSE mutation , *METHYL aspartate receptors , *GENE expression , *BRAIN diseases , *CELL lines , *PATIENTS , *NEURAL development , *CELL receptors , *DEVELOPMENTAL disabilities , *EPILEPSY , *GENETIC mutation , *NERVE tissue proteins , *VISION disorders , *CEREBRAL cortex abnormalities , *DISEASE risk factors - Abstract
Polymicrogyria is a malformation of cortical development. The aetiology of polymicrogyria remains poorly understood. Using whole-exome sequencing we found de novo heterozygous missense GRIN1 mutations in 2 of 57 parent-offspring trios with polymicrogyria. We found nine further de novo missense GRIN1 mutations in additional cortical malformation patients. Shared features in the patients were extensive bilateral polymicrogyria associated with severe developmental delay, postnatal microcephaly, cortical visual impairment and intractable epilepsy. GRIN1 encodes GluN1, the essential subunit of the N-methyl-d-aspartate receptor. The polymicrogyria-associated GRIN1 mutations tended to cluster in the S2 region (part of the ligand-binding domain of GluN1) or the adjacent M3 helix. These regions are rarely mutated in the normal population or in GRIN1 patients without polymicrogyria. Using two-electrode and whole-cell voltage-clamp analysis, we showed that the polymicrogyria-associated GRIN1 mutations significantly alter the in vitro activity of the receptor. Three of the mutations increased agonist potency while one reduced proton inhibition of the receptor. These results are striking because previous GRIN1 mutations have generally caused loss of function, and because N-methyl-d-aspartate receptor agonists have been used for many years to generate animal models of polymicrogyria. Overall, our results expand the phenotypic spectrum associated with GRIN1 mutations and highlight the important role of N-methyl-d-aspartate receptor signalling in the pathogenesis of polymicrogyria. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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22. Upregulation of HMGB1-TLR4 inflammatory pathway in focal cortical dysplasia type II.
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Zhang, Zhongbin, Liu, Qingzhu, Liu, Ming, Wang, Hui, Dong, Ying, Ji, Taoyun, Liu, Xiaoyan, Jiang, Yuwu, Cai, Lixin, and Wu, Ye
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DYSPLASIA , *CELL transformation , *CELLULAR pathology , *EPILEPSY , *BRAIN diseases , *CELL metabolism , *PROTEINS , *BIOCHEMISTRY , *BRAIN , *FOCAL cortical dysplasia , *NEURONS , *PHENOMENOLOGICAL biology , *CELL receptors , *NEURAL development , *CELLS , *RESEARCH funding , *INFLAMMATORY mediators , *CEREBRAL cortex abnormalities , *PHYSIOLOGY ,BRAIN metabolism - Abstract
Background: We attempted to determine whether the inflammatory pathway HMGB1-TLR4 and the downstream pro-inflammatory cytokines is upregulated in focal cortical dysplasia (FCD) type II and whether there is a correlation between the TLR4 upregulation and disease duration or frequency of epileptic seizures.Methods: FCD type II and peri-FCD paired tissues resected from eight children with refractory epilepsy were collected. Through real-time qPCR, Western blot, and co-immunoprecipitation, we examined the differences between FCD lesions and peri-FCD tissues with respect to mRNA expression, protein expression, and protein interaction in HMGB1-TLR4 pathway biomarker and downstream pro-inflammatory factors in whole brain tissue. Then, we used immunofluorescence to examine the difference between FCD lesions and peri-FCD tissues with respect to protein expression and intracellular distribution of HMGB1-TLR4 pathway biomarker in neurons, astrocytes, and oligodendrocytes. Correlation between level of TLR4 expression and disease duration or frequency of epileptic seizures in patients was also analyzed.Results: The protein expression levels of TLR4, cytoplasm HMGB1, TLR4/MyD88 complex, ubiquitination of TRAF6, p-IKK, p-IκB-α, p-NF-κB p65, and IL-1β and TNF-α in lesion tissues were significantly higher than those in peri-FCD controls. Total mRNA expression levels of TLR4, IL-1β, and TNF-α in lesion tissues were significantly higher than those in peri-FCD controls, but HMGB1 had no significant change. In neurons and astrocytes inside the lesions, the expression of TLR4 protein was significantly higher than that in peri-FCD tissues, and HMGB1 was mainly expressed in the cytoplasm, while expressed in the nuclei in peri-FCD tissues. But in oligodendrocytes, there was no upregulation of HMGB1-TLR4 pathway in both lesions and peri-FCD tissues. We did not identify the correlation between the level of TLR4 activation and disease duration or frequency of epileptic seizures.Conclusion: The HMGB1-TLR4 pathway was upregulated in the neurons and astrocytes inside FCD type II lesions, which led to an increase in the release of downstream pro-inflammatory cytokines. Correlation between the level of TLR4 activation and duration or frequency of epileptic seizures was not identified. [ABSTRACT FROM AUTHOR]- Published
- 2018
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23. Stereo- EEG: Diagnostic and therapeutic tool for periventricular nodular heterotopia epilepsies.
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Mirandola, Laura, Mai, Roberto F., Francione, Stefano, Pelliccia, Veronica, Gozzo, Francesca, Sartori, Ivana, Nobili, Lino, Cardinale, Francesco, Cossu, Massimo, Meletti, Stefano, and Tassi, Laura
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DIAGNOSIS of epilepsy , *ELECTROENCEPHALOGRAPHY , *ELECTROCOAGULATION (Medicine) , *MAGNETIC resonance imaging of the brain , *CEREBRAL cortex abnormalities , *NEUROSURGERY - Abstract
Objective Periventricular nodular heterotopias ( PNHs) are malformations of cortical development related to neuronal migration disorders, frequently associated with drug-resistant epilepsy ( DRE). Stereo-electroencephalography (SEEG) is considered a very effective step of the presurgical evaluation, providing the recognition of the epileptogenic zone ( EZ). At the same time, via the intracerebral electrodes it is possible to perform radiofrequency thermocoagulation ( SEEG-guided RF- TC) with the aim of ablating and/or disrupting the EZ. The purpose of this study was to evaluate both the relationships between PNH and the EZ, and the efficacy of SEEG-guided RF- TC. Methods Twenty patients with DRE related to PNHs were studied. Inclusion criteria were the following: (1) patients with epilepsy and PNHs (unilateral or bilateral, single or multiple nodules) diagnosed on brain magnetic resonance imaging ( MRI); (2) S EEG recordings available as part of the presurgical investigations, with at least one intracerebral electrode inside the heterotopia; (3) complete surgical workup with SEEG-guided RF- TC and/or with traditional neurosurgery, with a follow-up of at least 12 months. Results Complex and heterogenic epileptic networks were found in these patients. SEEG-guided RF- TC both into the nodules and/or the cortex was efficacious in the 76% of patients. Single or multiple, unilateral or bilateral PNHs are the most suitable for this procedure, whereas patients with PNHs associated with complex cortical malformations obtained excellent outcome only with traditional resective surgery. Significance Each patient had a specific epileptogenic network, independent from the number, size, or location of nodules and from the cortical malformation associated with. SEEG-guided RF- TC appears as a new and very effective diagnostic and therapeutic approach for DRE related to PNHs. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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24. Psychiatric behaviors associated with cytoskeletal defects in radial neuronal migration.
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Fukuda, Toshifumi and Yanagi, Shigeru
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PATHOLOGICAL psychology , *CYTOSKELETON , *CEREBRAL cortex abnormalities , *SCHIZOPHRENIA , *NEURON development , *AUTISM - Abstract
Normal development of the cerebral cortex is an important process for higher brain functions, such as language, and cognitive and social functions. Psychiatric disorders, such as schizophrenia and autism, are thought to develop owing to various dysfunctions occurring during the development of the cerebral cortex. Radial neuronal migration in the embryonic cerebral cortex is a complex process, which is achieved by strict control of cytoskeletal dynamics, and impairments in this process are suggested to cause various psychiatric disorders. Our recent findings indicate that radial neuronal migration as well as psychiatric behaviors is rescued by controlling microtubule stability during the embryonic stage. In this review, we outline the relationship between psychiatric disorders, such as schizophrenia and autism, and radial neuronal migration in the cerebral cortex by focusing on the cytoskeleton and centrosomes. New treatment strategies for psychiatric disorders will be discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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25. The spectrum of structural and functional network alterations in malformations of cortical development.
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Seok-Jun Hong, Bernhardt, Boris C., Gill, Ravnoor S., Bernasconi, Neda, Bernasconi, Andrea, and Hong, Seok-Jun
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BRAIN imaging , *NEUROPHYSIOLOGY , *NEURAL development , *DYSPLASIA , *DEVELOPMENTAL neurobiology , *CEREBRAL cortex , *EPILEPSY , *MAGNETIC resonance imaging , *NERVOUS system , *NERVOUS system abnormalities , *NEURORADIOLOGY , *POSITRON emission tomography , *CEREBRAL cortex abnormalities , *CASE-control method - Abstract
Neuroimaging studies of malformations of cortical development have mainly focused on the characterization of the primary lesional substrate, while whole-brain investigations remain scarce. Our purpose was to assess large-scale brain organization in prevalent cortical malformations. Based on experimental evidence suggesting that distributed effects of focal insults are modulated by stages of brain development, we postulated differential patterns of network anomalies across subtypes of malformations. We studied a cohort of patients with focal cortical dysplasia type II (n = 63), subcortical nodular heterotopia (n = 44), and polymicrogyria (n = 34), and compared them to 82 age- and sex-matched controls. Graph theoretical analysis of structural covariance networks indicated a consistent rearrangement towards a regularized architecture characterized by increased path length and clustering, as well as disrupted rich-club topology, overall suggestive of inefficient global and excessive local connectivity. Notably, we observed a gradual shift in network reconfigurations across subgroups, with only subtle changes in focal cortical dysplasia type II, moderate effects in heterotopia and maximal effects in polymicrogyria. Analysis of resting state functional connectivity also revealed gradual network changes, with most marked rearrangement in polymicrogyria; contrary to findings in the structural domain, however, functional architecture was characterized by decreases in both local and global parameters. Diverging results in the structural and functional domain were supported by formal structure-function coupling analysis. Our findings support the concept that time of insult during corticogenesis impacts the severity of topological network reconfiguration. Specifically, late-stage malformations, typified by polymicrogyria, may selectively disrupt the formation of large-scale cortico-cortical networks and thus lead to a more profound impact on whole-brain organization than early stage disturbances of predominantly radial migration patterns observed in cortical dysplasia type II, which likely affect a relatively confined cortical territory. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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26. An Unusual EEG Pattern Associated with a Complex Malformation of Cortical Development.
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Jyostna, Aruna Setumadhava, Vinayan, Kollencheri Puthenveettil, Anand, Vaishakh, Shridharani, Akash, and Ravindran, Sonu
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ELECTRODES , *ELECTROENCEPHALOGRAPHY , *MAGNETIC resonance imaging , *NEURAL development , *CEREBRAL cortex abnormalities , *CEREBRAL cortex - Published
- 2022
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27. Adult Hemimegalencephaly with Migraine as the First Symptom.
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Liu, Qian, Zhao, Wenjuan, and Zhou, Guanen
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NEURAL development , *CEREBRAL cortex abnormalities ,MIGRAINE complications - Abstract
Besides, we found her mini-mental state examination score was 18/30 (the patient was illiterate), and Montreal cognitive assessment score was 19/30. Magnetic resonance imaging (MRI) of the brain showed enlarged right hemisphere with smooth thickened cortex and pachygyria, indistinct gray/white differentiation. Discussion In this case, the patient presented with a contralateral headache rather than an ipsilateral headache. [Extracted from the article]
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- 2022
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28. Volume versus surface-based cortical thickness measurements: A comparative study with healthy controls and multiple sclerosis patients.
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Buck, D., Righart, R., Biberacher, V., Beer, A., Mühlau, M., Schmidt, P., Hemmer, B., Dahnke, R., Gaser, C., Kirschke, J. S., and Zimmer, C.
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CEREBRAL cortex , *MULTIPLE sclerosis diagnosis , *CEREBRAL cortex anatomy , *CEREBRAL cortex abnormalities , *MULTIPLE sclerosis treatment - Abstract
The cerebral cortex is a highly folded outer layer of grey matter tissue that plays a key role in cognitive functions. In part, alterations of the cortex during development and disease can be captured by measuring the cortical thickness across the whole brain. Available software tools differ with regard to labor intensity and computational demands. In this study, we compared the computational anatomy toolbox (CAT), a recently proposed volume-based tool, with the well-established surface-based tool FreeSurfer. We observed that overall thickness measures were highly inter-correlated, although thickness estimates were systematically lower in CAT than in FreeSurfer. Comparison of multiple sclerosis (MS) patients with age-matched healthy control subjects showed highly comparable clusters of MS-related thinning for both methods. Likewise, both methods yielded comparable clusters of age-related cortical thinning, although correlations between age and average cortical thickness were stronger for FreeSurfer. Our data suggest that, for the analysis of cortical thickness, the volume-based CAT tool can be regarded a considerable alternative to the well-established surface-based FreeSurfer tool. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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29. Malformations of cortical development: genetic mechanisms and diagnostic approach.
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Jeehun Lee
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HUMAN abnormalities , *CEREBRAL cortex abnormalities , *EPILEPSY - Abstract
Malformations of cortical development are rare congenital anomalies of the cerebral cortex, wherein patients present with intractable epilepsy and various degrees of developmental delay. Cases show a spectrum of anomalous cortical formations with diverse anatomic and morphological abnormalities, a variety of genetic causes, and different clinical presentations. Brain magnetic resonance imaging has been of great help in determining the exact morphologies of cortical malformations. The hypothetical mechanisms of malformation include interruptions during the formation of cerebral cortex in the form of viral infection, genetic causes, and vascular events. Recent remarkable developments in genetic analysis methods have improved our understanding of these pathological mechanisms. The present review will discuss normal cortical development, the current proposed malformation classifications, and the diagnostic approach for malformations of cortical development. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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30. Novel homozygous RARS2 mutation in two siblings without pontocerebellar hypoplasia - further expansion of the phenotypic spectrum.
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Lühl, S., Bode, H., Schlötzer, W., Bartsakoulia, M., Horvath, R., Abicht, A., Stenzel, M., Kirschner, J., and Grünert, S. C.
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CEREBRAL cortex abnormalities , *GENETIC mutation , *MITOCHONDRIAL pathology , *TRANSFER RNA synthetases , *GENETIC translation - Abstract
Background: Pontocerebellar hypoplasia type 6 (PCH6) is a mitochondrial disease caused by mutations in the RARS2 gene. RARS2 encodes mitochondrial arginyl transfer RNA synthetase, an enzyme involved in mitochondrial protein translation. A total of 27 patients from 14 families have been reported so far. Characteristic clinical features comprise neonatal lactic acidosis, severe encephalopathy, intractable seizures, feeding problems and profound developmental delay. Most patients show typical neuroradiologic abnormalities including cerebellar hypoplasia and progressive pontocerebellar atrophy. Methods: We describe the clinical, biochemical and molecular features of 2 siblings with a novel homozygous mutation in RARS2. Both patients presented neonatally with lactic acidosis. While the older sibling had severe neurological symptoms with microcephaly, seizures and developmental delay, the younger patient was still neurologically asymptomatic at the age of 2 months. Results: MRI studies in both children lacked pontocerebellar involvement. The expression of the OXPHOS complex proteins was decreased in both patients, whereas oxygen consumption was increased. Conclusions: Characteristic neuroradiological abnormalities of PCH6 such as vermis and cerebellar hypoplasia and progressive pontocerebellar atrophy may be missing in patients with RARS2 mutations. RARS2 testing should therefore also be performed in patients without pontocerebellar hypoplasia but otherwise typical clinical symptoms. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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31. Dysregulation of the (immuno)proteasome pathway in malformations of cortical development.
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van Scheppingen, J., Broekaart, D. W. M., Scholl, T., Zuidberg, M. R. J., Anink, J. J., Spliet, W. G., van Rijen, P. C., Czech, T., Hainfellner, J. A., Feucht, M., Mühlebner, A., van Vliet, E. A., and Aronica, E.
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PROTEASOMES , *MULTIENZYME complexes , *IMMUNOHISTOCHEMISTRY , *PROTEOLYSIS , *INFLAMMATION , *CELL metabolism , *CEREBRAL cortex abnormalities , *NEURAL development , *CELL culture , *CELLULAR signal transduction , *CEREBRAL cortex , *CYTOKINES , *EPILEPSY , *NERVE tissue proteins , *PROTEOLYTIC enzymes , *TUBEROUS sclerosis , *RAPAMYCIN , *LIPOPOLYSACCHARIDES , *PHARMACODYNAMICS - Abstract
Background: The proteasome is a multisubunit enzyme complex involved in protein degradation, which is essential for many cellular processes. During inflammation, the constitutive subunits are replaced by their inducible counterparts, resulting in the formation of the immunoproteasome.Methods: We investigated the expression pattern of constitutive (β1, β5) and immunoproteasome (β1i, β5i) subunits using immunohistochemistry in malformations of cortical development (MCD; focal cortical dysplasia (FCD) IIa and b, cortical tubers from patients with tuberous sclerosis complex (TSC), and mild MCD (mMCD)). Glial cells in culture were used to elucidate the mechanisms regulating immunoproteasome subunit expression.Results: Increased expression was observed in both FCD II and TSC; β1, β1i, β5, and β5i were detected (within cytosol and nucleus) in dysmorphic neurons, balloon/giant cells, and reactive astrocytes. Glial and neuronal nuclear expression positively correlated with seizure frequency. Positive correlation was also observed between the glial expression of constitutive and immunoproteasome subunits and IL-1β. Accordingly, the proteasome subunit expression was modulated by IL-1β in human astrocytes in vitro. Expression of both constitutive and immunoproteasome subunits in FCD II-derived astroglial cultures was negatively regulated by treatment with the immunomodulatory drug rapamycin (inhibitor of the mammalian target of rapamycin (mTOR) pathway, which is activated in both TSC and FCD II).Conclusions: These observations support the dysregulation of the proteasome system in both FCD and TSC and provide new insights on the mechanism of regulation the (immuno)proteasome in astrocytes and the molecular links between inflammation, mTOR activation, and epilepsy. [ABSTRACT FROM AUTHOR]- Published
- 2016
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32. Intracranial migrating bone dust: Innocuous or evil?
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Jaiswal, Palak, Vilanilam, George, Rajalakshmi, P, Kumar, Krishna, Abraham, Mathew, Jaiswal, Palak A, Vilanilam, George C, and Kumar, Krishna K
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EMPYEMA , *SURGICAL site infections , *DUST , *BONES , *EPILEPSY surgery , *NEURAL development , *SEIZURES (Medicine) , *CRANIOTOMY , *EDEMA , *EPILEPSY , *SKULL , *SPASMS , *SURGICAL complications , *TREATMENT effectiveness , *CEREBRAL cortex abnormalities , *DISEASE complications - Published
- 2019
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33. Neuro-MIG: A European network on brain malformations.
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Mancini, Grazia M.S.
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NEUROLOGICAL disorders , *BRAIN abnormalities , *CEREBRAL cortex abnormalities , *CEREBRAL palsy , *PHENOTYPES - Published
- 2018
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34. Congenital bilateral perisylvian syndrome.
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Chatur, Chinky and Balani, Ankit
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ELECTROENCEPHALOGRAPHY , *HYPERVENTILATION , *EPILEPSY , *MAGNETIC resonance imaging , *BRAIN , *NEURAL development , *CEREBRAL cortex , *PEOPLE with intellectual disabilities , *CEREBRAL cortex abnormalities , *SEVERITY of illness index , *MULTIPLE human abnormalities - Abstract
The article presents case study of a 12‑year old female patient who was diagnosed with Congenital bilateral perisylvian syndrome. It mentions that electroencephalography (EEG) revealed infrequent intermittent, irregular bursts of sharp waves which were generalized, bilaterally synchronous, present throughout the tracings in awake phases and triggered by hyperventilation, suggesting the presence of generalized epilepsy. It presents information on magnetic resonance imaging (MRI) of brain.
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- 2018
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35. Complex mode of inheritance in holoprosencephaly revealed by whole exome sequencing.
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Mouden, C., Dubourg, C., Carré, W., Rose, S., Quelin, C., Akloul, L., Hamdi‐Rozé, H., Viot, G., Salhi, H., Darnault, P., Odent, S., Dupé, V., and David, V.
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HOLOPROSENCEPHALY , *CEREBRAL cortex abnormalities , *CONGENITAL disorders , *GENETIC mutation , *HEREDITY , *GENETICS - Abstract
Holoprosencephaly ( HPE) is the most common congenital cerebral malformation, characterized by impaired forebrain cleavage and midline facial anomalies. Heterozygous mutations in 14 genes have been associated with HPE and are often inherited from an unaffected parent, underlying complex genetic bases. It is now emerging that HPE may result from a combination of multiple genetic events, rather than from a single heterozygous mutation. To explore this hypothesis, we undertook whole exome sequencing and targeted high-throughput sequencing approaches to identify mutations in HPE subjects. Here, we report two HPE families in which two mutations are implicated in the disease. In the first family presenting two foetuses with alobar and semi-lobar HPE, we found mutations in two genes involved in HPE, SHH and DISP1, inherited respectively from the father and the mother. The second reported case is a family with a 9-year-old girl presenting lobar HPE, harbouring two compound heterozygous mutations in DISP1. Together, these cases of digenic inheritance and autosomal recessive HPE suggest that in some families, several genetic events are necessary to cause HPE. This study highlights the complexity of HPE inheritance and has to be taken into account by clinicians to improve HPE genetic counselling. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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36. Cerebral cortex expansion and folding: what have we learned?
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Fernández, Virginia, Llinares‐Benadero, Cristina, and Borrell, Víctor
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CEREBRAL cortex abnormalities , *EMBRYOLOGY , *BRAIN function localization , *INTELLECTUAL disabilities , *COGNITION , *DEVELOPMENTAL neurobiology - Abstract
One of the most prominent features of the human brain is the fabulous size of the cerebral cortex and its intricate folding. Cortical folding takes place during embryonic development and is important to optimize the functional organization and wiring of the brain, as well as to allow fitting a large cortex in a limited cranial volume. Pathological alterations in size or folding of the human cortex lead to severe intellectual disability and intractable epilepsy. Hence, cortical expansion and folding are viewed as key processes in mammalian brain development and evolution, ultimately leading to increased intellectual performance and, eventually, to the emergence of human cognition. Here, we provide an overview and discuss some of the most significant advances in our understanding of cortical expansion and folding over the last decades. These include discoveries in multiple and diverse disciplines, from cellular and molecular mechanisms regulating cortical development and neurogenesis, genetic mechanisms defining the patterns of cortical folds, the biomechanics of cortical growth and buckling, lessons from human disease, and how genetic evolution steered cortical size and folding during mammalian evolution . [ABSTRACT FROM AUTHOR]
- Published
- 2016
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37. Downregulation of CD47 and CD200 in patients with focal cortical dysplasia type IIb and tuberous sclerosis complex.
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Fei-Ji Sun, Chun-Qing Zhang, Xin Chen, Yu-Jia Wei, Song Li, Shi-Yong Liu, Zhen-le Zang, Jiao-Jiang He, Wei Guo, Hui Yang, Sun, Fei-Ji, Zhang, Chun-Qing, Chen, Xin, Wei, Yu-Jia, Li, Song, Liu, Shi-Yong, Zang, Zhen-le, He, Jiao-Jiang, Guo, Wei, and Yang, Hui
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DYSPLASIA , *TUBEROUS sclerosis , *CHILDHOOD epilepsy , *CD47 antigen , *MICROGLIA , *CHILDREN with epilepsy , *CELL metabolism , *ANTIGENS , *BIOCHEMISTRY , *NEURAL development , *COMPARATIVE studies , *ENZYME-linked immunosorbent assay , *EPILEPSY , *IMMUNOHISTOCHEMISTRY , *PHENOMENOLOGY , *RESEARCH methodology , *MEDICAL cooperation , *NEURONS , *POLYMERASE chain reaction , *RESEARCH , *WESTERN immunoblotting , *EVALUATION research , *CEREBRAL cortex abnormalities , *METABOLISM ,BRAIN metabolism - Abstract
Background: Focal cortical dysplasia type IIb (FCD IIb) and tuberous sclerosis complex (TSC) are well-recognized causes of chronic intractable epilepsy in children. Accumulating evidence suggests that activation of the microglia/macrophage and concomitant inflammatory response in FCD IIb and TSC may contribute to the initiation and recurrence of seizures. The membrane glycoproteins CD47 and CD200, which are highly expressed in neurons and other cells, mediate inhibitory signals through their receptors, signal regulatory protein α (SIRP-α) and CD200R, respectively, in microglia/macrophages. We investigate the levels and expression pattern of CD47/SIRP-α and CD200/CD200R in surgically resected brain tissues from patients with FCD IIb and TSC, and the potential effect of soluble human CD47 Fc and CD200 Fc on the inhibition of several proinflammatory cytokines associated with FCD IIb and TSC in living epileptogenic brain slices in vitro. The level of interleukin-4 (IL-4), a modulator of CD200, was also investigated.Methods: Twelve FCD IIb (range 1.8-9.5 years), 13 TSC (range 1.5-10 years) patients, and 6 control cases (range 1.5-11 years) were enrolled. The levels of CD47/SIRP-α and CD200/CD200R were assessed by quantitative real-time polymerase chain reaction and western blot. The expression pattern of CD47/SIRP-α and CD200/CD200R was investigated by immunohistochemical analysis, and the cytokine concentrations were measured by enzyme-linked immune-sorbent assays.Results: Both the messenger RNA and protein levels of CD47, SIRP-α, and CD200, as well as the mRNA level of IL-4, were downregulated in epileptogenic lesions of FCD IIb and TSC compared with the control specimens, whereas CD200R levels were not significantly changed. CD47, SIRP-α, and CD200 were decreasingly expressed in dysmorphic neuron, balloon cells, and giant cells. CD47 Fc and CD200 Fc could inhibit IL-6 release but did not suppress IL-1β or IL-17 production.Conclusions: Our results suggest that microglial activation may be partially caused by CD47/SIRP-α- and CD200/CD200R-mediated reductions in the immune inhibitory pathways within FCD IIb and TSC cortical lesions where chronic neuroinflammation has been established. Upregulation or activation of CD47/SIRP-α and CD200/CD200R may have therapeutic potential for controlling neuroinflammation in human FCD IIb and TSC. [ABSTRACT FROM AUTHOR]- Published
- 2016
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38. Assessment transcallosal Diaschisis in a model of focal cerebral ischemia in rats.
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Arango-Dávila, César Augusto, Muñoz Ospina, Beatriz Elena, Manrique Castaño, Daniel, Potes, Laura, and Umbarila Prieto, John
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BRAIN injuries , *LABORATORY rats , *CEREBRAL cortex abnormalities , *BIOMARKERS ,ANIMAL models of cerebral ischemia - Abstract
Objective: To evaluate transcallosal changes after a local ischemic injury in rats by using the monoclonal marker anti-NeuN (Mouse anti-neuronal nuclei). Methods: Twenty eight adult, male, Wistar rats were subjected to focal injury in the right hemisphere. The technique used was the experimental model of focal ischemic injury through intraluminal suture of the middle cerebral artery. Analyses were made for the five groups: and after the lesion (control), at 24 h, 96 h, 10 days and 20 days. Exofocal neuronal damage was inferred from neuronal immunoreactivity changes to NeuN. Results: In the cortex contralateral to the lesion, immunoreactivity was diminished. This was most notable in the supragranular layers 24 h post ischemia. After 96 h, there was a generalized diminishment of the inmmunoreactivity in supra and infragranular layers. At 10 and 20 days, the tissue recovered some NeuN immunoreactivity, but there were set changes in the VI layer. Conclusion: The immunoreactive changes to NeuN support the process of interhemispheric diaschisis. Changes in immunoreactivity could indicate metabolic stress secondary to the disruption in connectivity to the site of lesion. [ABSTRACT FROM AUTHOR]
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- 2016
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39. Surgical management of symptomatic spinal cord and intracerebral cavernomas in a multiple cavernomas case.
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Gorgan, R.M., Brehar, F., Catana, M., Pruna, V., Gheorghiu, Ana, Popescu, G., Cristescu, Catioara, and Giovani, A.
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SPINAL cord abnormalities , *CEREBRAL cortex abnormalities , *SPINAL cord surgery , *FAMILIAL diseases , *MAGNETIC resonance imaging of the brain - Abstract
Multiple cavernous malformations are associated with familial cases and are present in 10-20% of all cavernoma cases. 5% of cavernomas are located intramedullary and of these only 10% present multiple cavernomas. With the availability of echo gradient MRI the cases of multiple cavernomas are diagnosed earlier and it is not rare that it uncovers multiple cavernomas in cases where only a single lesion can be identified on regular MRI sequences. We present the case of a 55 years old woman presented with a two years history of mild backache, followed by progressive lower legs motor deficit and urinary retention. The spine MRI showed an intramedullary T2/3 lesion and the cerebral MRI established the diagnosis of multiple cavernomas. One year after the intramedullary cavernoma was operated with success, she developed generalized seizures and a new cerebral MRI showed bleeding and volume growth of one right temporal pole cavernoma. The cerebral lesion was resected successfully and the patient was discharged free of seizures. This familial type multiple cavernomas cases should be screened and followed with repeated brain and spine MRI's every year. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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40. Cortical morphological markers in children with autism: a structural magnetic resonance imaging study of thickness, area, volume, and gyrification.
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Yang, Daniel Y.-J., Beam, Danielle, Pelphrey, Kevin A., Abdullahi, Sebiha, and Jou, Roger J.
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AUTISM in children , *CEREBRAL cortex abnormalities , *BIOMARKERS - Abstract
Background: Individuals with autism spectrum disorder (ASD) have been characterized by altered cerebral cortical structures; however, the field has yet to identify consistent markers and prior studies have included mostly adolescents and adults. While there are multiple cortical morphological measures, including cortical thickness, surface area, cortical volume, and cortical gyrification, few single studies have examined all these measures. The current study analyzed all of the four measures and focused on pre-adolescent children with ASD. Methods: We employed the FreeSurfer pipeline to examine surface-based morphometry in 60 high-functioning boys with ASD (mean age = 8.35 years, range = 4-12 years) and 41 gender-, age-, and IQ-matched typically developing (TD) peers (mean age = 8.83 years), while testing for age-by-diagnosis interaction and between-group differences. Results: During childhood and in specific regions, ASD participants exhibited a lack of normative age-related cortical thinning and volumetric reduction and an abnormal age-related increase in gyrification. Regarding surface area, ASD and TD exhibited statistically comparable age-related development during childhood. Across childhood, ASD relative to TD participants tended to have higher mean levels of gyrification in specific regions. Within ASD, those with higher Social Responsiveness Scale total raw scores tended to have greater age-related increase in gyrification in specific regions during childhood. Conclusions: ASD is characterized by cortical neuroanatomical abnormalities that are age-, measure-, statistical model-, and region-dependent. The current study is the first to examine the development of all four cortical measures in one of the largest pre-adolescent samples. Strikingly, Neurosynth-based quantitative reverse inference of the surviving clusters suggests that many of the regions identified above are related to social perception, language, self-referential, and action observation networks-those frequently found to be functionally altered in individuals with ASD. The comprehensive, multilevel analyses across a wide range of cortical measures help fill a knowledge gap and present a complex but rich picture of neuroanatomical developmental differences in children with ASD. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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41. Effects of Mecp2 loss of function in embryonic cortical neurons: a bioinformatics strategy to sort out non-neuronal cells variability from transcriptome profiling.
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Vacca, Marcella, Tripathi, Kumar Parijat, Speranza, Luisa, Cigliano, Riccardo Aiese, Scalabrì, Francesco, Marracino, Federico, Madonna, Michele, Sanseverino, Walter, Perrone-Capano, Carla, Guarracino, Mario Rosario, and D'Esposito, Maurizio
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RETT syndrome , *BIOINFORMATICS , *NEUROLOGICAL disorders , *CEREBRAL cortex abnormalities , *MORPHOMETRICS , *ANIMAL disease models - Abstract
Background: Mecp2 null mice model Rett syndrome (RTT) a human neurological disorder affecting females after apparent normal pre- and peri-natal developmental periods. Neuroanatomical studies in cerebral cortex of RTT mouse models revealed delayed maturation of neuronal morphology and autonomous as well as non-cell autonomous reduction in dendritic complexity of postnatal cortical neurons. However, both morphometric parameters and high-resolution expression profile of cortical neurons at embryonic developmental stage have not yet been studied. Here we address these topics by using embryonic neuronal primary cultures from Mecp2 loss of function mouse model. Results: We show that embryonic primary cortical neurons of Mecp2 null mice display reduced neurite complexity possibly reflecting transcriptional changes. We used RNA-sequencing coupled with a bioinformatics comparative approach to identify and remove the contribution of variable and hard to quantify non-neuronal brain cells present in our in vitro cell cultures. Conclusions: Our results support the need to investigate both Mecp2 morphological as well as molecular effect in neurons since prenatal developmental stage, long time before onset of Rett symptoms. [ABSTRACT FROM AUTHOR]
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- 2016
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42. The histopathology of polymicrogyria: a series of 71 brain autopsy studies.
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Jansen, Anna C, Robitaille, Yves, Honavar, Mrinalini, Mullatti, Nandini, Leventer, Richard J, Andermann, Eva, Andermann, Frederick, and Squier, Waney
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HUMAN abnormalities , *FETAL abnormalities , *MEDICAL records , *NEUROLOGICAL disorders , *BRAIN abnormalities , *AUTOPSY , *BRAIN , *NEURAL development , *RESEARCH funding , *CEREBRAL cortex abnormalities - Abstract
Aim: Polymicrogyria (PMG) is one of the most common forms of cortical malformation yet the mechanism of its development remains unknown. This study describes the histopathological aspects of PMG in a large series including a significant proportion of fetal cases.Method: We have reviewed the neuropathology and medical records of 44 fetuses and 27 children and adults in whom the cortical architecture was focally or diffusely replaced by one or more festooning bands of neurons.Results: The pial surface of the brain overlying the polymicrogyric cortex was abnormal in almost 90% of cases irrespective of the aetiology. This accords with animal studies indicating the importance of the leptomeninges in cortical development. The aetiology of PMG was highly heterogeneous and there was no correlation between cortical layering patterns and aetiology. PMG was almost always associated with other brain malformations.Interpretation: The inclusion of many fetal cases has allowed us to examine the early developmental stages of PMG. The study indicates the significance of surface signals responsible for human corticogenesis and the complex interaction between genetic and environmental factors leading to this common endpoint of cortical maldevelopment. [ABSTRACT FROM AUTHOR]- Published
- 2016
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43. Cortical thickness in de novo patients with Parkinson disease and mild cognitive impairment with consideration of clinical phenotype and motor laterality.
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Danti, S., Toschi, N., Diciotti, S., Tessa, C., Poletti, M., Del Dotto, P., and Lucetti, C.
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CEREBRAL cortex abnormalities , *PARKINSON'S disease patients , *MILD cognitive impairment , *PHENOTYPES , *CEREBRAL dominance , *CEREBRAL atrophy , *MAGNETIC resonance imaging - Abstract
Background and purpose Parkinson's disease ( PD) is a progressive neurodegenerative disorder with motor and non-motor symptoms, including cognitive deficits. Several magnetic resonance imaging approaches have been applied to investigate brain atrophy in PD. The aim of this study was to detect early structural cortical and subcortical changes in de novo PD whilst distinguishing cognitive status, clinical phenotype and motor laterality. Methods Eighteen de novo PD with mild cognitive impairment ( PD- MCI), 18 de novo PD without MCI ( PD- NC) and 18 healthy control subjects were evaluated. In the PD- MCI group, nine were tremor dominant and nine were postural instability gait disorder ( PIGD) phenotype; 11 had right-sided symptom dominance and seven had left-sided symptom dominance. FreeSurfer was used to measure cortical thickness/folding, subcortical structures and to study group differences as well as the association with clinical and neuropsychological data. Results Parkinson's disease with MCI showed regional thinning in the right frontal, right middle temporal areas and left insula compared to PD- NC. A reduction of the volume of the left and right thalamus and left hippocampus was found in PD- MCI compared to PD- NC. PD- MCI PIGD showed regional thinning in the right inferior parietal area compared to healthy controls. A decreased volume of the left thalamus was reported in PD- MCI with right-sided symptom dominance compared to PD- NC and PD- MCI with left-sided symptom dominance. Conclusions When MCI was present, PD patients showed a fronto-temporo-parietal pattern of cortical thinning. This cortical pattern does not appear to be influenced by motor laterality, although one-sided symptom dominance may contribute to volumetric reduction of specific subcortical structures. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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44. Bridging Cytoarchitectonics and Connectomics in Human Cerebral Cortex.
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van den Heuvel, Martijn P., Scholtens, Lianne H., Barrett, Lisa Feldman, Hilgetag, Claus C., and de Reus, Marcel A.
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CYTOARCHITECTONICS , *ANTERIOR corticospinal tract , *CEREBRAL cortex abnormalities , *CELL anatomy , *DIFFUSION magnetic resonance imaging , *DENDRITES - Abstract
The rich variation in cytoarchitectonics of the human cortex is well known to play an important role in the differentiation of cortical information processing, with functional multimodal areas noted to display more branched, more spinous, and an overall more complex cytoarchitecture. In parallel, connectome studies have suggested that also the macroscale wiring profile of brain areas may have an important contribution in shaping neural processes; for example, multimodal areas have been noted to display an elaborate macroscale connectivity profile. However, how these two scales of brain connectivity are related--and perhaps interact--remains poorly understood. In this communication, we combined data from the detailed mappings of early twentieth century cytoarchitectonic pioneers Von Economo and Koskinas (1925) on the microscale cellular structure of the human cortex with data on macroscale connectome wiring as derived from high-resolution diffusion imaging data from the Human Connectome Project. In a cross-scale examination, we show evidence of a significant association between cytoarchitectonic features of human cortical organization--in particular the size of layer 3 neurons--and whole-brain corticocortical connectivity. Our findings suggest that aspects of microscale cytoarchitectonics and macroscale connectomics are related. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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45. Congenital and Acquired Conditions of the Mesial Temporal Lobe: A Pictorial Essay.
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Ochoa-Escudero, Martin, Herrera, Diego A., Vargas, Sergio A., and Dublin, Arthur B.
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BRAIN anatomy , *NEURAL development , *CEREBROSPINAL fluid , *ENCEPHALITIS , *EPILEPSY , *HIPPOCAMPUS (Brain) , *INFLAMMATION , *NEURORADIOLOGY , *RADIOGRAPHY , *TEMPORAL lobe , *TUMORS , *CEREBRAL cortex abnormalities - Abstract
Purpose: Our goal is to pictorially review a wide spectrum of congenital and acquired conditions affecting the medial aspect of the temporal lobe. Conclusion: After completing this article, the reader will have knowledge of the imaging appearance of diverse developmental, malformative, and acquired lesions of the mesial temporal lobe, which will be useful when evaluating pathology in this location. [ABSTRACT FROM AUTHOR]
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- 2015
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46. Calcium-binding proteins in focal cortical dysplasia.
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Kuchukhidze, Giorgi, Wieselthaler‐Hölzl, Anna, Drexel, Meinrad, Unterberger, Iris, Luef, Gerhard, Ortler, Martin, Becker, Albert J., Trinka, Eugen, and Sperk, Günther
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DYSPLASIA , *CALCIUM-binding proteins , *CEREBRAL cortex abnormalities , *GABA , *TEMPORAL lobe epilepsy , *PARVALBUMINS - Abstract
Objective Alterations in γ-aminobutyric acid ( GABA)-ergic cortical neurons have been reported in focal cortical dysplasia ( FCD)Ia/ IIIa, a malformation of cortical development associated with drug-resistant epilepsy. We compared numbers of neurons containing calcium-binding proteins parvalbumin ( PV), calbindin ( CB), and calretinin ( CR) and densities of respective fibers in lateral temporal lobe surgical specimens of 17 patients with FCD with 19 patients who underwent anterior temporal lobe resection due to nonlesional temporal lobe epilepsy (non- FCD) as well as with 7 postmortem controls. Methods PV-, CB-, and CR-immunoreactive ( IR) neurons were quantitatively investigated with use of two-dimensional cell counting and densitometry (reflecting mainly IR fibers) in cortical layers II, IV, and V. Results Numbers of PV- IR neurons, ratios of PV-containing to Nissl-stained neurons (correcting for eventual cell loss), and densities of PV- IR were higher in layer II of the cortex of FCD compared to non- FCD patients. Similarly, densities of CB- IR and CR- IR were also higher in layers II and V, respectively, of FCD than of non- FCD patients. Comparison with postmortem controls revealed significant higher cell numbers and fiber labeling for all three calcium-binding proteins in FCD cortex, whereas numbers of Nissl-stained neurons did not vary between FCD, non- FCD, and postmortem controls. In non- FCD versus postmortem controls, ratios of calcium-binding protein- IR cells to Nissl-stained neurons were unchanged in most instances except for increased CB/Nissl ratios and CB- IR densities in all cortical layers. Significance Increased numbers of PV neurons and fiber labeling in FCD compared to nondysplastic epileptic temporal neocortex and postmortem controls may be related to cortical malformation, whereas an increased number of CB- IR neurons and fiber labeling both in FCD and non- FCD specimens compared with postmortem controls may be associated with ongoing seizure activity. The observed changes may represent increased expression of calcium-binding proteins and thus compensatory mechanisms for seizures and neuronal loss in drug-resistant epilepsy. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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47. Ictal and interictal Arterial Spin Labelling (ASL) in hemimegalencephaly.
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Thakor, Bina, Deshmukh, Yogeshwari, Jagtap, Sujit, and Kurwale, Nilesh
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CEREBRAL hemispheres , *CEREBRAL circulation , *MAGNETIC resonance imaging , *NEURAL development , *SINGLE-photon emission computed tomography , *SEIZURES (Medicine) , *CEREBRAL cortex abnormalities - Abstract
The article describes the case of a one-month-old baby without any perinatal insult presented with left focal seizures since day 12 of life. Topics discussed include the use of ictal and interictal single photon emission-computed tomography (SPECT) and positron imaging tomography (PET) to detect metabolic changes related to epileptic activity, information on arterial spin labelling (ASL), and reason that the cerebral blood flow (CBF) is typically increased in the acute peri-ictal period.
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- 2021
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48. Malformations of Cortical Development: A Structural and Functional MRI Perspective.
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Hogan, R. Edward
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CEREBRAL cortex abnormalities , *FUNCTIONAL magnetic resonance imaging , *BRAIN imaging , *NEURAL circuitry , *DYSPLASIA - Published
- 2018
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49. Transmantle Heterotopia or Closed Lip Schizencehaly: A Diagnostic Dilemma.
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Nayyar, Nishant, Sood, Dinesh, Kapila, Preeti T., Chauhan, Narvir S., and Patial, Varsha
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GRAY matter (Nerve tissue) , *EPILEPSY , *MAGNETIC resonance imaging , *NEURAL development , *CEREBRAL cortex abnormalities , *SEIZURES (Medicine) , *CEREBROSPINAL fluid , *CEREBRAL cortex - Abstract
The article presents a case study of a 41‑year‑old adult male presented with two episodes of generalized tonic clonic seizures. It mentions Transmantle heterotopia, a rare entity in which gray matter is seen extending from the ventricular wall to overlying cortex without intervening white matter or cerebrospinal fluid (CSF) cleft; and also mentions transmantle heterotopia in the right cerebral hemisphere with focal subcortical heterotopia in the contralateral hemisphere.
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- 2021
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50. Endogenous Neural Stem/Progenitor Cells Stabilize the Cortical Microenvironment after Traumatic Brain Injury.
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Dixon, Kirsty J., Theus, Michelle H., Nelersa, Claudiu M., Mier, Jose, Travieso, Lissette G., Yu, Tzong-Shiue, Kernie, Steven G., and Liebl, Daniel J.
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BRAIN injuries , *NEURAL stem cells , *PROGENITOR cells , *CEREBRAL cortex abnormalities , *DEVELOPMENTAL neurobiology , *CELL death - Abstract
Although a myriad of pathological responses contribute to traumatic brain injury (TBI), cerebral dysfunction has been closely linked to cell death mechanisms. A number of therapeutic strategies have been studied in an attempt to minimize or ameliorate tissue damage; however, few studies have evaluated the inherent protective capacity of the brain. Endogenous neural stem/progenitor cells (NSPCs) reside in distinct brain regions and have been shown to respond to tissue damage by migrating to regions of injury. Until now, it remained unknown whether these cells have the capacity to promote endogenous repair. We ablated NSPCs in the subventricular zone to examine their contribution to the injury microenvironment after controlled cortical impact (CCI) injury. Studies were performed in transgenic mice expressing the herpes simplex virus thymidine kinase gene under the control of the nestinδ promoter exposed to CCI injury. Two weeks after CCI injury, mice deficient in NSPCs had reduced neuronal survival in the perilesional cortex and fewer Iba-1-positive and glial fibrillary acidic protein-positive glial cells but increased glial hypertrophy at the injury site. These findings suggest that the presence of NSPCs play a supportive role in the cortex to promote neuronal survival and glial cell expansion after TBI injury, which corresponds with improvements in motor function. We conclude that enhancing this endogenous response may have acute protective roles after TBI. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
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