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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 -
Brain & Development Jan 2017To characterise the early tissue changes of post encephaloclastic polymicrogyria in the human fetus.
OBJECTIVE
To characterise the early tissue changes of post encephaloclastic polymicrogyria in the human fetus.
METHODS
We identified and reviewed the clinical histories and autopsy pathology of post ischemic fetal cerebral cortical injury at less than 30weeks gestational age (GA). The histology of local cortical abnormalities was examined with neuronal, glial, microglial and vascular immunohistochemical markers.
RESULTS
We identified eight cases ranging from 18 to 29weeks GA: 5 cases show full thickness cortical infarcts and 3 show periSylvian post-ischemic necrosis of the cerebral cortex. The maximal age is less than 10weeks after injury. There are abnormalities in gross fissuration as early as one month after injury. Disruption of the pia limitans was associated with a microglial and glial response and full thickness cortical injury. Macrophages were often seen accumulating deep to abnormal cortex. Hyperplasia of the subpial granular cell layer was universal in perilesional cortex. Cajal Retzius neuron hyperplasia, aggregation, and both superficial and deep displacement were noted. Where there was loss and dispersal of early cortical pyramidal neurons there was usually no pseudolaminar necrosis. Radial glia by 18weeks GA showed altered growth patterns and lateral branching. Altered migration of primitive elements was often prominent. Particularly prior to 20weeks GA subadjacent subplate neurons showed striking hypertrophy.
CONCLUSIONS
The array of histological changes encompasses all tissue elements of the affected brains, early in the evolution polymicrogyria. Although subpial alterations were ubiquitous, not all changes are referable to alterations in the pia limitans. The role of the necroinflammatory response in the genesis of abnormal cytoarchitecture deserves further study.
Topics: Brain; Cerebral Infarction; Humans; Immunohistochemistry; Macrophages; Neuroglia; Polymicrogyria
PubMed: 27406708
DOI: 10.1016/j.braindev.2016.06.005 -
Neurology Mar 2016We explored the long-term follow-up of continuous spike-and-wave complexes during sleep (CSWS) in polymicrogyria and the anatomic volumetric variables that influence the...
OBJECTIVE
We explored the long-term follow-up of continuous spike-and-wave complexes during sleep (CSWS) in polymicrogyria and the anatomic volumetric variables that influence the risk of developing this age-related epileptic encephalopathy.
METHODS
We performed prospective follow-up of 27 patients with polymicrogyria/CSWS (mean follow-up 14.3 years; range 2-31 years) and comparative volumetric analysis of the polymicrogyric hemispheres and ipsilateral thalami vs 3 subgroups featuring polymicrogyria without CSWS, benign rolandic epilepsy (BRE), and headache. Receiver operator characteristic analysis of the power of volumetric values was determined to predict CSWS.
RESULTS
CSWS peaked between 5 and 7 years (mean age at onset 4.7 years). Remission occurred within 2 years from onset in 21%, within 4 years in 50%, and by age 13 years in 100%. We found smaller thalamic and hemispheric volumes in polymicrogyria/CSWS with respect to polymicrogyria without CSWS (p = 0.0021 for hemispheres; p = 0.0003 for thalami), BRE, and controls with headache (p < 0.0001). Volumes of the malformed hemispheres and ipsilateral thalami reliably identified the risk of incurring CSWS, with a 68-fold increased risk for values lower than optimal diagnostic cutoffs (436,150 mm(3) for malformed hemispheres or 4,616 mm(3) for ipsilateral thalami; sensitivity 92.54%; specificity 84.62%). The risk increased by 2% for every 1,000 mm(3) reduction of the polymicrogyric hemispheres and by 15% for every 100 mm(3) reduction of ipsilateral thalami.
CONCLUSIONS
The polymicrogyria/CSWS syndrome is likely caused by a cortico-thalamic malformation complex and is characterized by remission of epilepsy within early adolescence. Early assessment of hemispheric and thalamic volumes in children with polymicrogyria and epilepsy can reliably predict CSWS.
Topics: Action Potentials; Child; Child, Preschool; Electroencephalography; Epilepsy, Rolandic; Female; Follow-Up Studies; Humans; Infant; Male; Polymicrogyria; Prospective Studies; Sleep Stages; Syndrome; Thalamus
PubMed: 26944271
DOI: 10.1212/WNL.0000000000002526 -
AJNR. American Journal of Neuroradiology Dec 2023The current imaging assessment of fetal brain gyrification is performed qualitatively and subjectively using sonography and MR imaging. A few previous studies have...
BACKGROUND AND PURPOSE
The current imaging assessment of fetal brain gyrification is performed qualitatively and subjectively using sonography and MR imaging. A few previous studies have suggested methods for quantification of fetal gyrification based on 3D reconstructed MR imaging, which requires unique data and is time-consuming. In this study, we aimed to develop an automatic pipeline for gyrification assessment based on routinely acquired fetal 2D MR imaging data, to quantify normal changes with gestation, and to measure differences in fetuses with lissencephaly and polymicrogyria compared with controls.
MATERIALS AND METHODS
We included coronal T2-weighted MR imaging data of 162 fetuses retrospectively collected from 2 clinical sites: 134 controls, 12 with lissencephaly, 13 with polymicrogyria, and 3 with suspected lissencephaly based on sonography, yet with normal MR imaging diagnoses. Following brain segmentation, 5 gyrification parameters were calculated separately for each hemisphere on the basis of the area and ratio between the contours of the cerebrum and its convex hull. Seven machine learning classifiers were evaluated to differentiate control fetuses and fetuses with lissencephaly or polymicrogyria.
RESULTS
In control fetuses, all parameters changed significantly with gestational age ( < .05). Compared with controls, fetuses with lissencephaly showed significant reductions in all gyrification parameters ( ≤ .02). Similarly, significant reductions were detected for fetuses with polymicrogyria in several parameters ( ≤ .001). The 3 suspected fetuses showed normal gyrification values, supporting the MR imaging diagnosis. An XGBoost-linear algorithm achieved the best results for classification between fetuses with lissencephaly and control fetuses ( = 32), with an area under the curve of 0.90 and a recall of 0.83. Similarly, a random forest classifier showed the best performance for classification of fetuses with polymicrogyria and control fetuses ( = 33), with an area under the curve of 0.84 and a recall of 0.62.
CONCLUSIONS
This study presents a pipeline for automatic quantification of fetal brain gyrification and provides normal developmental curves from a large cohort. Our method significantly differentiated fetuses with lissencephaly and polymicrogyria, demonstrating lower gyrification values. The method can aid radiologic assessment, highlight fetuses at risk, and may improve early identification of fetuses with cortical malformations.
Topics: Female; Humans; Polymicrogyria; Retrospective Studies; Brain; Magnetic Resonance Imaging; Lissencephaly; Fetus
PubMed: 38050002
DOI: 10.3174/ajnr.A8046 -
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 -
Neurobiology of Disease Nov 2022Malformations of cortical development (MCDs) are common causes of drug-resistant epilepsy. The mechanisms underlying the associated epileptogenesis and ictogenesis... (Review)
Review
OBJECTIVES
Malformations of cortical development (MCDs) are common causes of drug-resistant epilepsy. The mechanisms underlying the associated epileptogenesis and ictogenesis remain poorly elucidated. EEG can help in understanding these mechanisms. We systematically reviewed studies reporting scalp or intracranial EEG features of MCDs to characterise interictal and seizure-onset EEG patterns across different MCD types.
METHODS
We conducted a systematic review in accordance with PRISMA guidelines. MEDLINE, PubMed, and Cochrane databases were searched for studies describing interictal and seizure-onset EEG patterns in MCD patients. A classification framework was implemented to group EEG features into 20 predefined patterns, comprising nine interictal (five, scalp EEG; four, intracranial EEG) and 11 seizure-onset (five, scalp EEG; six, intracranial EEG) patterns. Logistic regression was used to estimate the odds ratios (OR) of each seizure-onset pattern being associated with specific MCD types.
RESULTS
Our search yielded 1682 studies, of which 27 comprising 936 MCD patients were included. Of the nine interictal EEG patterns, five (three, scalp EEG; two, intracranial EEG) were detected in ≥2 MCD types, while four (rhythmic epileptiform discharges type 1 and type 2 on scalp EEG; repetitive bursting spikes and sporadic spikes on intracranial EEG) were seen only in focal cortical dysplasia (FCD). Of the 11 seizure-onset patterns, eight (three, scalp EEG; five, intracranial EEG) were found in ≥2 MCD types, whereas three were observed only in FCD (suppression on scalp EEG; delta brush on intracranial EEG) or tuberous sclerosis complex (TSC; focal fast wave on scalp EEG). Among scalp EEG seizure-onset patterns, paroxysmal fast activity (OR = 0.13; 95% CI: 0.03-0.53; p = 0.024) and repetitive epileptiform discharges (OR = 0.18; 95% CI: 0.05-0.61; p = 0.036) were less likely to occur in TSC than FCD. Among intracranial EEG seizure-onset patterns, low-voltage fast activity was more likely to be detected in heterotopia (OR = 19.3; 95% CI: 6.22-60.1; p < 0.001), polymicrogyria (OR = 6.70; 95% CI: 2.25-20.0; p = 0.004) and TSC (OR = 4.27; 95% CI: 1.88-9.70; p = 0.005) than FCD.
SIGNIFICANCE
Different MCD types can share similar interictal or seizure-onset EEG patterns, reflecting common underlying biological mechanisms. However, selected EEG patterns appear to point to distinct MCD types, suggesting certain differences in their neuronal networks.
Topics: Humans; Electrocorticography; Electroencephalography; Magnetic Resonance Imaging; Malformations of Cortical Development; Seizures; Tuberous Sclerosis
PubMed: 36165814
DOI: 10.1016/j.nbd.2022.105863 -
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 -
Pediatric Neurology Nov 2017The 22q11.2 deletion syndrome affects multiple organ systems, and the neurological manifestations are an important aspect of this disorder. Many are aware of cardiac... (Review)
Review
BACKGROUND
The 22q11.2 deletion syndrome affects multiple organ systems, and the neurological manifestations are an important aspect of this disorder. Many are aware of cardiac anomalies associated with this uncommon genetic disorder. However, the different types of seizures, electroencephalography (EEG), and brain magnetic resonance imaging (MRI) findings seen in this condition are not appreciated.
METHODS
Medical records of four patients with epilepsy due to 22q11.2 deletion syndrome were retrospectively reviewed for documentation of seizure types, EEG, and brain MRI findings. In addition, we also did a literature review of previously reported individuals with unprovoked seizures in this condition.
RESULTS
A review of all published cases including our patients reveals that focal epilepsy (39 of 88, 44%) is the most common type followed by genetic generalized epilepsy (24 of 88, 27%). Diffuse cerebral atrophy and polymicrogyria were the most frequent MRI findings.
CONCLUSIONS
Patients with structural brain abnormalities, especially polymicrogyria and associated epilepsy should have a chromosomal microarray (CMA) performed to screen for the 22q11.2 deletion syndrome. Focal epilepsy and genetic generalized epilepsy are the most frequent epilepsy types reported in this condition.
Topics: Adolescent; Adult; Brain; Child; Child, Preschool; DiGeorge Syndrome; Epilepsy; Humans; Magnetic Resonance Imaging; Male
PubMed: 28969878
DOI: 10.1016/j.pediatrneurol.2017.08.011 -
Frontiers in Neuroscience 2015Neuronal migration disorders are human (or animal) diseases that result from a disruption in the normal movement of neurons from their original birth site to their final... (Review)
Review
Neuronal migration disorders are human (or animal) diseases that result from a disruption in the normal movement of neurons from their original birth site to their final destination during early development. As a consequence, the neurons remain somewhere along their migratory route, their location depending on the pathological mechanism and its severity. The neurons form characteristic abnormalities, which are morphologically classified into several types, such as lissencephaly, heterotopia, and cobblestone dysplasia. Polymicrogyria is classified as a group of malformations that appear secondary to post-migration development; however, recent findings of the underlying molecular mechanisms reveal overlapping processes in the neuronal migration and post-migration development stages. Mutations of many genes are involved in neuronal migration disorders, such as LIS1 and DCX in classical lissencephaly spectrum, TUBA1A in microlissencephaly with agenesis of the corpus callosum, and RELN and VLDLR in lissencephaly with cerebellar hypoplasia. ARX is of particular interest from basic and clinical perspectives because it is critically involved in tangential migration of GABAergic interneurons in the forebrain and its mutations cause a variety of phenotypes ranging from hydranencephaly or lissencephaly to early-onset epileptic encephalopathies, including Ohtahara syndrome and infantile spasms or intellectual disability with no brain malformations. The recent advances in gene and genome analysis technologies will enable the genetic basis of neuronal migration disorders to be unraveled, which, in turn, will facilitate genotype-phenotype correlations to be determined.
PubMed: 26052266
DOI: 10.3389/fnins.2015.00181 -
Topics in Magnetic Resonance Imaging :... Feb 2019In congenital Zika virus syndrome (CZS), the most frequent radiological findings are calcifications in the cortical-white matter junction and malformations of cortical... (Review)
Review
In congenital Zika virus syndrome (CZS), the most frequent radiological findings are calcifications in the cortical-white matter junction and malformations of cortical development (pachygyria or polymicrogyria, which occur predominantly in the frontal lobes, or a simplified gyral pattern), ventriculomegaly, enlargement of the cisterna magna and the extra-axial subarachnoid space, corpus callosum abnormalities, and reduced brain volume. This syndrome can also result in a decrease in the brainstem and cerebellum volumes and delayed myelination. Infants with CZS may show venous thrombosis and lenticulostriate vasculopathies. Over a 3-year follow-up period, many infants with CZS showed hydrocephalus, reduction in brain calcifications, and greater reduction in brain thickness.
Topics: Brain; Calcinosis; Diagnostic Imaging; Female; Humans; Hydrocephalus; Infant; Infant, Newborn; Magnetic Resonance Imaging; Microcephaly; Nervous System Malformations; Pregnancy; Pregnancy Complications, Infectious; Syndrome; Tomography, X-Ray Computed; Ultrasonography, Prenatal; Zika Virus; Zika Virus Infection
PubMed: 30817674
DOI: 10.1097/RMR.0000000000000193