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Journal of Neuropathology and... Aug 2022
Topics: Humans; Magnetic Resonance Imaging; Malformations of Cortical Development; Mutation; Neurons; Polymicrogyria
PubMed: 35788683
DOI: 10.1093/jnen/nlac052 -
Neuroradiology Jun 2010Polymicrogyria is one of the most common malformations of cortical development. It has been known for many years and its clinical and MRI manifestations are well... (Review)
Review
Polymicrogyria is one of the most common malformations of cortical development. It has been known for many years and its clinical and MRI manifestations are well described. Recent advances in imaging, however, have revealed that polymicrogyria has many different appearances on MR imaging, suggesting that is may be a more heterogeneous malformation than previously suspected. The clinical and imaging heterogeneity of polymicrogyria is explored in this review.
Topics: Brain; Humans; Magnetic Resonance Imaging; Malformations of Cortical Development
PubMed: 20198472
DOI: 10.1007/s00234-009-0644-2 -
Journal of Medical Genetics May 2005Polymicrogyria is a relatively common malformation of cortical development, characterised by multiple small gyri with abnormal cortical lamination. The different forms... (Review)
Review
Polymicrogyria is a relatively common malformation of cortical development, characterised by multiple small gyri with abnormal cortical lamination. The different forms of polymicrogyria encompass a wide range of clinical, aetiological, and histological findings. Advances in imaging have improved the diagnosis and classification of the condition. The molecular basis of polymicrogyria is beginning to be elucidated with the identification of a gene, GPR56, for bilateral frontoparietal polymicrogyria. Functional studies of the GPR56 gene product will yield insights not only into the causes of polymicrogyria but also into the mechanisms of normal cortical development and the regional patterning of the cerebral cortex. Based on imaging studies, several other region specific patterns of polymicrogyria have been identified, and there is increasing evidence that these may also have a significant genetic component to their aetiology. This paper reviews current knowledge of the different polymicrogyria syndromes, with discussion of clinical and imaging features, patterns of inheritance, currently mapped loci, candidate genes, chromosomal abnormalities, and implications for genetic counselling.
Topics: Cerebral Cortex; Chromosome Aberrations; Genetic Counseling; Humans; Intellectual Disability; Magnetic Resonance Imaging; Nervous System Malformations; Syndrome
PubMed: 15863665
DOI: 10.1136/jmg.2004.023952 -
Pediatric Neurology Mar 2021The ratio between excitatory (glutamatergic) and inhibitory (GABAergic) inputs into maturing individual cortical neurons influences their epileptic potential. Structural... (Review)
Review
BACKGROUND
The ratio between excitatory (glutamatergic) and inhibitory (GABAergic) inputs into maturing individual cortical neurons influences their epileptic potential. Structural factors during development that alter synaptic inputs can be demonstrated neuropathologically. Increased mitochondrial activity identifies neurons with excessive discharge rates.
METHODS
This study focuses on the neuropathological examinaion of surgical resections for epilepsy and at autopsy, in fetuses, infants, and children, using immunocytochemical markers, and electron microscopy in selected cases. Polymicrogyria and Down syndrome are highlighted.
RESULTS
Factors influencing afferent synaptic ratios include the following: (1) synaptic short-circuitry in fused molecular zones of adjacent gyri (polymicrogyria); (2) impaired development of dendritic spines decreasing excitation (Down syndrome); (3) extracellular keratan sulfate proteoglycan binding to somatic membranes but not dendritic spines may be focally diminished (cerebral atrophy, schizencephaly, lissencephaly, polymicrogyria) or augmented, ensheathing individual axons (holoprosencephaly), or acting as a barrier to axonal passage in the U-fiber layer. If keratan is diminished, glutamate receptors on the neuronal soma enable ectopic axosomatic excitatory synapses to form; (4) dysplastic, megalocytic neurons and balloon cells in mammalian target of rapamycin disorders; (5) satellitosis of glial cells displacing axosomatic synapses; (6) peri-neuronal inflammation (tuberous sclerosis) and heat-shock proteins.
CONCLUSIONS
Synaptic ratio of excitatory/inhibitory afferents is a major fundamental basis of epileptogenesis at the neuronal level. Neuropathology can demonstrate subcellular changes that help explain either epilepsy or lack of seizures in immature brains. Synaptic ratios in malformations influence postnatal epileptogenesis. Single neurons can be hypermetabolic and potentially epileptogenic.
Topics: Down Syndrome; Epilepsy; Fetus; Humans; Infant, Newborn; Malformations of Cortical Development; Neurons, Afferent; Polymicrogyria; Synapses
PubMed: 33450624
DOI: 10.1016/j.pediatrneurol.2020.11.001 -
Epilepsy Research Sep 2011Polymicrogyria is a cerebral cortical malformation characterized by an excessively folded cortical ribbon of miniature and individually thin convolutions. Although... (Review)
Review
Polymicrogyria is a cerebral cortical malformation characterized by an excessively folded cortical ribbon of miniature and individually thin convolutions. Although polymicrogyria is a highly epileptogenic lesion, its epileptogenic mechanism is unclear. The anomalous cortex associated with polymicrogyria includes less excitable neural tissue such as a cell sparse zone, but involves a part of a larger epileptic network extending to adjacent cortical areas. This malformation can be modeled in rats with a transcortical prenatal or neonatal freeze lesion, which mimics the histological characteristics of a human four-layered polymicrogyria. Several hypotheses have so far been presented for seizure susceptibility in polymicrogyria, including alterations of glutamate receptor distribution, abnormalities in ion channels, new excitatory or inhibitory connections, and downregulation of GABA(A) receptor subunits. The cortical hyperexcitability in polymicrogyria may be reduced by the inhibitory neuronal network. Further detailed investigations of a population with aberrantly migrating inhibitory interneurons will provide novel and important insights into the pathogenetic mechanisms of epilepsy in polymicrogyria.
Topics: Animals; Disease Models, Animal; Disease Susceptibility; Epilepsy; Humans; Malformations of Cortical Development; Rats; Receptors, GABA-A; Receptors, Glutamate
PubMed: 21733659
DOI: 10.1016/j.eplepsyres.2011.06.010 -
Journal of Psychiatric Practice Sep 2023Secondary mania refers to a manic episode that arises during a medical illness other than bipolar disorder or in response to a drug or medication. As the...
BACKGROUND
Secondary mania refers to a manic episode that arises during a medical illness other than bipolar disorder or in response to a drug or medication. As the psychopathological features of secondary mania resemble those of mania due to bipolar disorder, misdiagnosis is frequent.
PURPOSE AND BASIC PROCEDURES
We present the case of a 20-year-old woman who developed a manic episode with psychotic symptoms, in whom polymicrogyria, a malformation of the cortical development with abnormal electroencephalographic activity, was documented. After initiating antiepileptic management, the affective symptoms completely subsided.
MAIN FINDINGS
To date, no specific recommendations are available concerning when to perform advanced studies in patients with a manic episode; however, as our case shows, these are much needed.
PRINCIPAL CONCLUSION
Because the treatment of secondary conditions largely depends on finding the underlying cause, patients with a new-onset mania should undergo a thorough assessment for secondary causes.
Topics: Female; Humans; Young Adult; Adult; Mania; Polymicrogyria; Bipolar Disorder; Affective Symptoms; Anticonvulsants
PubMed: 37678371
DOI: 10.1097/PRA.0000000000000728 -
The Journal of Neuroscience Nursing :... Oct 2009Polymicrogyria is one of several neuronal migrational defects. This disorder is derived from a malformation in cortical development characterized by many small gyri,... (Review)
Review
Polymicrogyria is one of several neuronal migrational defects. This disorder is derived from a malformation in cortical development characterized by many small gyri, shallow sulci, and abnormal cortical layering. The potential causes of polymicrogyria include genetic disorders, intrauterine cytomegalovirus infection, and fetal vascular supply disruption. A wide variation in the extent of findings exists, ranging from minor deficits to profound neurological dysfunction. Seizures, feeding problems, elimination, physical mobility, and psychosocial issues must be managed for children with polymicrogyria. Children with this disorder require collaborative care from healthcare practitioners and parents to achieve their highest level of health. The incidence of neuronal migrational defects is approximately 1 in 2,500 live births (L. Villard et al., 2002). The diagnosis of these disorders has increased with improvement of magnetic resonance imaging (MRI) technology (A. J. Barkovich, R. Hevner, & R. Guerrini, 1999).
Topics: Anticonvulsants; Child; Humans; Malformations of Cortical Development; Pediatric Nursing
PubMed: 19835238
DOI: 10.1097/jnn.0b013e3181aaa97a -
American Journal of Medical Genetics.... Feb 2022
Topics: Basal Ganglia; Brain; Humans; Mutation; Polymicrogyria; Sodium-Potassium-Exchanging ATPase
PubMed: 34633143
DOI: 10.1002/ajmg.a.62531 -
Epilepsia Apr 2021We sought to identify novel genes and to establish the contribution of known genes in a large cohort of patients with nonsyndromic sporadic polymicrogyria and epilepsy.
OBJECTIVE
We sought to identify novel genes and to establish the contribution of known genes in a large cohort of patients with nonsyndromic sporadic polymicrogyria and epilepsy.
METHODS
We enrolled participants with polymicrogyria and their parents through the Epilepsy Phenome/Genome Project. We performed phenotyping and whole exome sequencing (WES), trio analysis, and gene-level collapsing analysis to identify de novo or inherited variants, including germline or mosaic (postzygotic) single nucleotide variants, small insertion-deletion (indel) variants, and copy number variants present in leukocyte-derived DNA.
RESULTS
Across the cohort of 86 individuals with polymicrogyria and epilepsy, we identified seven with pathogenic or likely pathogenic variants in PIK3R2, including four germline and three mosaic variants. PIK3R2 was the only gene harboring more than expected de novo variants across the entire cohort, and likewise the only gene that passed the genome-wide threshold of significance in the gene-level rare variant collapsing analysis. Consistent with previous reports, the PIK3R2 phenotype consisted of bilateral polymicrogyria concentrated in the perisylvian region with macrocephaly. Beyond PIK3R2, we also identified one case each with likely causal de novo variants in CCND2 and DYNC1H1 and biallelic variants in WDR62, all genes previously associated with polymicrogyria. Candidate genetic explanations in this cohort included single nucleotide de novo variants in other epilepsy-associated and neurodevelopmental disease-associated genes (SCN2A in two individuals, GRIA3, CACNA1C) and a 597-kb deletion at 15q25, a neurodevelopmental disease susceptibility locus.
SIGNIFICANCE
This study confirms germline and postzygotically acquired de novo variants in PIK3R2 as an important cause of bilateral perisylvian polymicrogyria, notably with macrocephaly. In total, trio-based WES identified a genetic diagnosis in 12% and a candidate diagnosis in 6% of our polymicrogyria cohort. Our results suggest possible roles for SCN2A, GRIA3, CACNA1C, and 15q25 deletion in polymicrogyria, each already associated with epilepsy or other neurodevelopmental conditions without brain malformations. The role of these genes in polymicrogyria will be further understood as more patients with polymicrogyria undergo genetic evaluation.
Topics: Child; Child, Preschool; Cohort Studies; Epilepsy; Female; Genetic Predisposition to Disease; Genetic Variation; Humans; Male; Phosphatidylinositol 3-Kinases; Polymicrogyria
PubMed: 33818783
DOI: 10.1111/epi.16854 -
Life (Basel, Switzerland) May 2022This paper describes the contemporary state of knowledge regarding processes that regulate normal development of the embryonic-fetal central nervous system (CNS). The... (Review)
Review
This paper describes the contemporary state of knowledge regarding processes that regulate normal development of the embryonic-fetal central nervous system (CNS). The processes are described according to the developmental timetable: dorsal induction, ventral induction, neurogenesis, neuronal migration, post-migration neuronal development, and cortical organization. We review the current literature on CNS malformations associated with these regulating processes. We specifically address neural tube defects, holoprosencephaly, malformations of cortical development (including microcephaly, megalencephaly, lissencephaly, cobblestone malformations, gray matter heterotopia, and polymicrogyria), disorders of the corpus callosum, and posterior fossa malformations. Fetal ventriculomegaly, which frequently accompanies these disorders, is also reviewed. Each malformation is described with reference to the etiology, genetic causes, prenatal sonographic imaging, associated anomalies, differential diagnosis, complimentary diagnostic studies, clinical interventions, neurodevelopmental outcome, and life quality.
PubMed: 35743840
DOI: 10.3390/life12060809