-
AJNR. American Journal of Neuroradiology Feb 2015Polymicrogyria is a malformation of cortical development that is often identified in children with epilepsy or delayed development. We investigated in vivo the potential...
BACKGROUND AND PURPOSE
Polymicrogyria is a malformation of cortical development that is often identified in children with epilepsy or delayed development. We investigated in vivo the potential of 7T imaging in characterizing polymicrogyria to determine whether additional features could be identified.
MATERIALS AND METHODS
Ten adult patients with polymicrogyria previously diagnosed by using 3T MR imaging underwent additional imaging at 7T. We assessed polymicrogyria according to topographic pattern, extent, symmetry, and morphology. Additional imaging sequences at 7T included 3D T2* susceptibility-weighted angiography and 2D tissue border enhancement FSE inversion recovery. Minimum intensity projections were used to assess the potential of the susceptibility-weighted angiography sequence for depiction of cerebral veins.
RESULTS
At 7T, we observed perisylvian polymicrogyria that was bilateral in 6 patients, unilateral in 3, and diffuse in 1. Four of the 6 bilateral abnormalities had been considered unilateral at 3T. While 3T imaging revealed 2 morphologic categories (coarse, delicate), 7T susceptibility-weighted angiography images disclosed a uniform ribbonlike pattern. Susceptibility-weighted angiography revealed numerous dilated superficial veins in all polymicrogyric areas. Tissue border enhancement imaging depicted a hypointense line corresponding to the gray-white interface, providing a high definition of the borders and, thereby, improving detection of the polymicrogyric cortex.
CONCLUSIONS
7T imaging reveals more anatomic details of polymicrogyria compared with 3T conventional sequences, with potential implications for diagnosis, genetic studies, and surgical treatment of associated epilepsy. Abnormalities of cortical veins may suggest a role for vascular dysgenesis in pathogenesis.
Topics: Adolescent; Adult; Cerebral Angiography; Cerebral Cortex; Child; Child, Preschool; Epilepsy; Female; Humans; Imaging, Three-Dimensional; Infant; Magnetic Resonance Imaging; Male; Middle Aged; Neuroimaging; Polymicrogyria
PubMed: 25258368
DOI: 10.3174/ajnr.A4116 -
AJNR. American Journal of Neuroradiology Nov 2021MR imaging studies and neuropathologic findings in individuals with 22q11.2 deletion syndrome show anomalous early brain development. We aimed to retrospectively...
BACKGROUND AND PURPOSE
MR imaging studies and neuropathologic findings in individuals with 22q11.2 deletion syndrome show anomalous early brain development. We aimed to retrospectively evaluate cerebral abnormalities, focusing on gray matter heterotopia, and to correlate these with subjects' neuropsychiatric impairments.
MATERIALS AND METHODS
Three raters assessed gray matter heterotopia and other morphologic brain abnormalities on 3D T1WI and T2*WI in 75 individuals with 22q11.2 deletion syndrome (27 females, 15.5 [SD, 7.4] years of age) and 53 controls (24 females, 12.6 [SD, 4.7] years of age). We examined the association among the groups' most frequent morphologic findings, general cognitive performance, and comorbid neuropsychiatric conditions.
RESULTS
Heterotopia in the white matter were the most frequent finding in individuals with 22q11.2 deletion syndrome ( = 29; controls, = 0; between-group difference, < .001), followed by cavum septi pellucidi and/or vergae ( = 20; controls, = 0; < .001), periventricular cysts ( = 10; controls, = 0; = .007), periventricular nodular heterotopia ( = 10; controls, = 0; = .007), and polymicrogyria ( = 3; controls, = 0; = .3). However, individuals with these morphologic brain abnormalities did not differ significantly from those without them in terms of general cognitive functioning and psychiatric comorbidities.
CONCLUSIONS
Taken together, our findings, periventricular nodular heterotopia or heterotopia in the white matter (possibly related to interrupted Arc cells migration), persistent cavum septi pellucidi and/or vergae, and formation of periventricular cysts, give clues to the brain development disorder induced by the 22q11.2 deletion syndrome. There was no evidence that these morphologic findings were associated with differences in psychiatric or cognitive presentation of the 22q11.2 deletion syndrome.
Topics: Brain; DiGeorge Syndrome; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Periventricular Nodular Heterotopia; Retrospective Studies
PubMed: 34620586
DOI: 10.3174/ajnr.A7283 -
Journal of Neurosurgery. Case Lessons May 2023Schizencephaly is an uncommon central nervous system malformation. Intracranial lipomas are also rare, accounting for approximately 0.1% of brain "tumors." They are...
BACKGROUND
Schizencephaly is an uncommon central nervous system malformation. Intracranial lipomas are also rare, accounting for approximately 0.1% of brain "tumors." They are believed to be derived from a persistent meninx primitiva, a neural crest-derived mesenchyme that develops into the dura and leptomeninges.
OBSERVATIONS
The authors present a case of heterotopic adipose tissue and a nonshunting arterial vascular malformation arising within a schizencephalic cleft in a 22-year-old male. Imaging showed right frontal gray matter abnormality and an associated suspected arteriovenous malformation with evidence of hemorrhage. Brain magnetic resonance imaging revealed right frontal polymicrogyria lining an open-lip schizencephaly, periventricular heterotopic gray matter, fat within the schizencephalic cleft, and gradient echo hypointensity concerning for prior hemorrhage. Histological assessment demonstrated mature adipose tissue with large-bore, thick-walled, irregular arteries. Mural calcifications and subendothelial cushions suggesting nonlaminar blood flow were observed. There were no arterialized veins or direct transitions from the arteries to veins. Hemosiderin deposition was scant, and hemorrhage was not present. The final diagnosis was consistent with ectopic mature adipose tissue and arteries with meningocerebral cicatrix.
LESSONS
This example of a complex maldevelopment of derivatives of the meninx primitiva in association with cortical maldevelopment highlights the unique challenges from both a radiological and histological perspective during diagnostic workup.
PubMed: 37218736
DOI: 10.3171/CASE2388 -
Disease Models & Mechanisms Oct 2021Within the past 20 years, particularly with the advent of exome sequencing technologies, autosomal dominant and de novo mutations in the gene encoding the...
Within the past 20 years, particularly with the advent of exome sequencing technologies, autosomal dominant and de novo mutations in the gene encoding the neurone-specific α3 subunit of the Na+,K+-ATPase (NKA α3) pump, ATP1A3, have been identified as the cause of a phenotypic continuum of rare neurological disorders. These allelic disorders of ATP1A3 include (in approximate order of severity/disability and onset in childhood development): polymicrogyria; alternating hemiplegia of childhood; cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing loss syndrome; relapsing encephalopathy with cerebellar ataxia; and rapid-onset dystonia-parkinsonism. Some patients present intermediate, atypical or combined phenotypes. As these disorders are currently difficult to treat, there is an unmet need for more effective therapies. The molecular mechanisms through which mutations in ATP1A3 result in a broad range of neurological symptoms are poorly understood. However, in vivo comparative studies using genetically altered model organisms can provide insight into the biological consequences of the disease-causing mutations in NKA α3. Herein, we review the existing mouse, zebrafish, Drosophila and Caenorhabditis elegans models used to study ATP1A3-related disorders, and discuss their potential contribution towards the understanding of disease mechanisms and development of novel therapeutics.
Topics: Animals; Animals, Genetically Modified; Disease Models, Animal; Humans; Mutation; Nervous System Diseases; Sodium-Potassium-Exchanging ATPase
PubMed: 34612482
DOI: 10.1242/dmm.048938 -
AJNR. American Journal of Neuroradiology Aug 2020Polymicrogyria and lissencephaly may be associated with abnormal organization of the undelying white matter tracts that have been rarely investigated so far. Our aim was...
BACKGROUND AND PURPOSE
Polymicrogyria and lissencephaly may be associated with abnormal organization of the undelying white matter tracts that have been rarely investigated so far. Our aim was to characterize white matter tract organization in polymicrogyria and lissencephaly using constrained spherical deconvolution, a multifiber diffusion MR imaging modeling technique for white matter tractography reconstruction.
MATERIALS AND METHODS
We retrospectively reviewed 50 patients (mean age, 8.3 ± 5.4 years; range, 1.4-21.2 years; 27 males) with different polymicrogyria ( = 42) and lissencephaly ( = 8) subtypes. The fiber direction-encoded color maps and 6 different white matter tracts reconstructed from each patient were visually compared with corresponding images reconstructed from 7 age-matched, healthy control WM templates. Each white matter tract was assessed by 2 experienced pediatric neuroradiologists and scored in consensus on the basis of the severity of the structural abnormality, ranging from the white matter tracts being absent to thickened. The results were summarized by different polymicrogyria and lissencephaly subgroups.
RESULTS
More abnormal-appearing white matter tracts were identified in patients with lissencephaly compared with those with polymicrogyria (79.2% versus 37.3%). In lissencephaly, structural abnormalities were identified in all studied white matter tracts. In polymicrogyria, the more frequently affected white matter tracts were the cingulum, superior longitudinal fasciculus, inferior longitudinal fasciculus, and optic radiation-posterior corona radiata. The severity of superior longitudinal fasciculus and cingulum abnormalities was associated with the polymicrogyria distribution and extent. A thickened superior fronto-occipital fasciculus was demonstrated in 3 patients.
CONCLUSIONS
We demonstrated a range of white matter tract structural abnormalities in patients with polymicrogyria and lissencephaly. The patterns of white matter tract involvement are related to polymicrogyria and lissencephaly subgroups, distribution, and, possibly, their underlying etiologies.
Topics: Adolescent; Brain; Child; Child, Preschool; Diffusion Tensor Imaging; Female; Humans; Infant; Lissencephaly; Male; Polymicrogyria; Retrospective Studies; White Matter; Young Adult
PubMed: 32732266
DOI: 10.3174/ajnr.A6646 -
Neurology Jan 2019Hereditary hemorrhagic telangiectasia (HHT) is generally considered a disorder of endothelial dysfunction, characterized by the development of multiple systemic...
Hereditary hemorrhagic telangiectasia (HHT) is generally considered a disorder of endothelial dysfunction, characterized by the development of multiple systemic arteriovenous malformations (AVMs), including within the brain. However, there have recently been a number of reports correlating HHT with malformations of cortical development, of which polymicrogyria is the most common type. Here we present 7 new cases demonstrating polymicrogyria in HHT, 6 of which demonstrate a brain AVM (bAVM) in close spatial proximity, with the aim of providing a common origin for the association. Upon reviewing patient genetics and imaging data and comparing with previously reported findings, we form 2 new conclusions: (1) polymicrogyria in HHT appears exclusively associated with a subset of mutations in the transmembrane protein endoglin that is involved with blood flow-related mechanotransduction signaling during angiogenesis and (2) the polymicrogyria is characteristically unilateral, typically focal, and correlates with vascular regions experiencing low fluid shear stress during corticogenesis in utero. Integrating these with findings in the literature from genetics and molecular biology experiments, we propose a theory suggesting haploinsufficient endoglin mutations, especially those that are dominant-negative, may predispose focal, aberrant hypersprouting angiogenesis during corticogenesis that leads to the production of polymicrogyria. This hypoxic insult may further serve as the revealing trigger for later development of a spatially coincident bAVM. This hypothesis suggests an essential role for endoglin-mediated hemodynamic mechanotransduction in normal corticogenesis.
Topics: Adolescent; Adult; Arteriovenous Malformations; Brain; Child; Child, Preschool; Female; Humans; Infant; Male; Polymicrogyria; Telangiectasia, Hereditary Hemorrhagic
PubMed: 30584075
DOI: 10.1212/WNL.0000000000006686 -
British Journal of Clinical Pharmacology Dec 2022To evaluate the number and nature of reported congenital malformations (CMs) after intrauterine exposure to non-tumour necrosis factor inhibitor biologics (non-TNFi...
AIMS
To evaluate the number and nature of reported congenital malformations (CMs) after intrauterine exposure to non-tumour necrosis factor inhibitor biologics (non-TNFi biologics) compared to certolizumab pegol (CZP).
METHODS
A retrospective comparative study was conducted in the EudraVigilance (EV) database. A safe biologic (CZP) was considered as the reference group. Odds ratios (ORs) for CMs were calculated for each non-TNFi biologic (including abatacept, anakinra, belimumab, ixekizumab, rituximab, secukinumab, tocilizumab, ustekinumab and vedolizumab), versus CZP (quantitative assessment). Then, CM patterns were reviewed in consultation with a clinical geneticist (qualitative assessment).
RESULTS
ORs were not statistically significant except for belimumab and vedolizumab (similar in magnitude). Except for vedolizumab, no specific CM patterns were observed for the included non-TNFi biologics. Three cases of corpus callosum agenesis (CCA) were identified for vedolizumab (versus none in CZP and other investigated non-TNFi biologics). Two of the CCA cases were associated with other neurological CMs (one cerebral ventriculomegaly with microcephaly and one polymicrogyria). This may indicate that these CCAs are related to undiagnosed genetic alterations or are associated with the underlying maternal disease, although a definite relationship with vedolizumab exposure cannot be ruled out.
CONCLUSION
No special safety signal was identified regarding the occurrence of CMs after exposure to abatacept (n = 64), anakinra (n = 20), belimumab (n = 93), ixekizumab (n = 29), rituximab (n = 57), secukinumab (n = 128), tocilizumab (n = 124) and ustekinumab (n = 215). Regarding observed CCAs in the vedolizumab group (n = 113), no firm conclusions can be made based on available information.
Topics: Humans; Abatacept; Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Certolizumab Pegol; Interleukin 1 Receptor Antagonist Protein; Necrosis; Retrospective Studies; Rituximab; Tumor Necrosis Factor-alpha; Ustekinumab
PubMed: 35894810
DOI: 10.1111/bcp.15471 -
Seizure Mar 2021Report of the contribution of invasive EEG (iEEG) and epileptogenicity mappings (EM) in a pediatric cohort of patients with epilepsy associated with focal polymicrogyria...
OBJECTIVE
Report of the contribution of invasive EEG (iEEG) and epileptogenicity mappings (EM) in a pediatric cohort of patients with epilepsy associated with focal polymicrogyria (PMG) and candidates for resective surgery.
METHOD
Retrospective pediatric case series of patients presenting focal PMG-related refractory epilepsy undergoing an invasive exploration (iEEG) at Fondation Rothschild Hospital. We reviewed clinical data, structural MRI, and visual analysis of iEEG recordings. Moreover, time-frequency analysis of SEEG signals with a neuroimaging approach (epileptogenicity maps) was used to support visual analysis.
RESULTS
Between 2012 and 2019, eight patients were selected. Five patients were explored with stereoelectroencephalography (SEEG) only, one patient with subdural exploration (SDE) only and two patients first underwent SEEG and then SDE. The mean age at seizure onset was 40.3 months (range 3-120), and the mean age for the iEEG 10.8 years (range 7-15). The epileptogenic zone (EZ) appeared concordant to the PMG lesion in only one case, was larger in three cases, smaller in two cases and different in one case. Four cases were selected for tailored resective surgery and one for total callosotomy. Two patients remained seizure-free at their last follow-up (mean 32.6 months, range 7-98). Epileptogenicity mapping (EM) refined the qualitative analysis, showing in four patients an EZ larger than visually defined.
CONCLUSION
This study is the first pediatric study to analyze the value of iEEG and EM as well as operability in focal PMG-related refractory epilepsy. The results illustrate the complexity of this pathology with variable concordance between the EZ and the lesion and mixed response to surgery.
Topics: Adolescent; Child; Child, Preschool; Drug Resistant Epilepsy; Electroencephalography; Humans; Infant; Polymicrogyria; Retrospective Studies; Stereotaxic Techniques
PubMed: 33517238
DOI: 10.1016/j.seizure.2021.01.010 -
Dialogues in Clinical Neuroscience 2008Malformations of cortical development (MCDs) are macroscopic or microscopic abnormalities of the cerebral cortex that arise as a consequence of an interruption to the... (Review)
Review
Malformations of cortical development (MCDs) are macroscopic or microscopic abnormalities of the cerebral cortex that arise as a consequence of an interruption to the normal steps of formation of the cortical plate. The human cortex develops its basic structure during the first two trimesters of pregnancy as a series of overlapping steps, beginning with proliferation and differentiation of neurons, which then migrate before finally organizing themselves in the developing cortex. Abnormalities at any of these stages, be they environmental or genetic in origin, may cause disruption of neuronal circuitry and predispose to a variety of clinical consequences, the most common of which is epileptic seizures. A large number of MCDs have now been described, each with characteristic pathological, clinical, and imaging features. The causes of many of these MCDs have been determined through the study of affected individuals, with many MCDs now established as being secondary to mutations in cortical development genes. This review will highlight the best-known of the human cortical malformations associated with epilepsy. The pathological, clinical, imaging, and etiologic features of each MCD will be summarized, with representative magnetic resonance imaging (MRI) images shown for each MCD. The malformations tuberous sclerosis, focal cortical dysplasia, hemimegalencephaly, classical lissencephaly, subcortical band heterotopia, periventricular nodular heterotopia, polymicrogyria, and schizencephaly will be presented.
Topics: Cell Movement; Cerebral Cortex; Epilepsy; Humans; Lissencephaly; Malformations of Cortical Development; Nervous System Malformations; Periventricular Nodular Heterotopia; Tuberous Sclerosis
PubMed: 18472484
DOI: 10.31887/DCNS.2008.10.1/rjleventer -
Molecular Syndromology Dec 2023We report on a 4-year-old female patient who presented with severe intellectual disability, autistic features, hyperlaxity of joints, and progressive scoliosis....
INTRODUCTION
We report on a 4-year-old female patient who presented with severe intellectual disability, autistic features, hyperlaxity of joints, and progressive scoliosis. Whole-exome sequencing identified a de novo missense variant (c.976C>T; p.Arg326Cys) in .
CASE PRESENTATION
The girl was born with congenital diaphragmatic hernia a finding which had not previously been associated with variants in . Her brain MRI showed hypogenesis of corpus callosum, ventriculomegaly, frontal and perisylvian polymicrogyria, and hypoplastic pons in addition to Dandy-Walker malformation.
CONCLUSION
Our results confirmed the phenotype and genotype correlation of missense variants and the polymicrogyria. Moreover, it further expands the knowledge of the phenotypic and molecular features of related intellectual disability.
PubMed: 38058759
DOI: 10.1159/000531715