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Neurology India 2023Incomplete hippocampal inversion (IHI) is a developmental failure of normal hippocampal inversion. Previous studies have described IHI in epilepsy and non-epilepsy...
BACKGROUND AND PURPOSE
Incomplete hippocampal inversion (IHI) is a developmental failure of normal hippocampal inversion. Previous studies have described IHI in epilepsy and non-epilepsy subjects. IHI has also been reported with malformations of cortical development (MCDs) and corpus callosal agenesis that have association with neuropsychiatric disorders such as autism spectrum disorder (ASD). This study aims to describe the clinical profile of magnetic resonance imaging (MRI)-diagnosed IHI.
MATERIALS AND METHODS
We studied patients with IHI who were identified after a retrospective review of the MRI archives of the past 3 years. The MRI findings of partial and total IHI were included. The clinical profiles associated with IHI were classified into epilepsy and non-epilepsy categories.
RESULTS
A retrospective review of MRI done over 3 years revealed 54 cases of IHI (32 left-sided, 20 bilateral, and 2 isolated right-sided), and out of 74 IHI, 59 were of total type and 15 partial. Thirty-six subjects (61.1%) had epilepsy (9 with neurodevelopmental problems), 17 subjects (31.5%) had ASD, and 4 subjects (7.4%) had only neurodevelopmental disorders. MCDs were seen in 7 (12.9%): polymicrogyria (4), periventricular heterotopia (2), and pachygyria (1). Hippocampal volume loss was seen in 10, and contralateral mesial temporal sclerosis was seen in 2 patients.
CONCLUSION
Hippocampal inversion has been reported in MRI scans of patients with epilepsy, ASD, MCDs, and many other related disorders. Further studies are required to know its occurrence among patients who get MRI scans due to many other disorders such as headaches, psychiatric disorders, minor hear trauma, and perinatal insults. If possible, studies among normal populations also need to be done.
Topics: Humans; Autism Spectrum Disorder; Hippocampus; Epilepsy; Magnetic Resonance Imaging; Neuroimaging
PubMed: 38174460
DOI: 10.4103/0028-3886.391380 -
Developmental Cell Dec 2023The cerebral cortex-the brain's covering and largest region-has increased in size and complexity in humans and supports higher cognitive functions such as language and... (Review)
Review
The cerebral cortex-the brain's covering and largest region-has increased in size and complexity in humans and supports higher cognitive functions such as language and abstract thinking. There is a growing understanding of the human cerebral cortex, including the diversity and number of cell types that it contains, as well as of the developmental mechanisms that shape cortical structure and organization. In this review, we discuss recent progress in our understanding of molecular and cellular processes, as well as mechanical forces, that regulate the folding of the cerebral cortex. Advances in human genetics, coupled with experimental modeling in gyrencephalic species, have provided insights into the central role of cortical progenitors in the gyrification and evolutionary expansion of the cerebral cortex. These studies are essential for understanding the emergence of structural and functional organization during cortical development and the pathogenesis of neurodevelopmental disorders associated with cortical malformations.
Topics: Humans; Cerebral Cortex; Brain; Biological Evolution; Neurogenesis
PubMed: 38113850
DOI: 10.1016/j.devcel.2023.11.004 -
Cortex; a Journal Devoted To the Study... Feb 2024The absence of speech is a clinical phenotype seen across neurodevelopmental syndromes, offering insights for neural language models. We present a case of bilateral...
The absence of speech is a clinical phenotype seen across neurodevelopmental syndromes, offering insights for neural language models. We present a case of bilateral perisylvian polymicrogyria (BPP) and complete absence of speech with considerable language comprehension and production difficulties. We extensively characterized the auditory speech perception and production circuitry by employing a multimodal neuroimaging approach. Results showed extensive cortical thickening in motor and auditory-language regions. The auditory cortex lacked sensitivity to speech stimuli despite relatively preserved thalamic projections yet had no intrinsic functional organization. Subcortical structures implicated in early stages of processing exhibited heightened sensitivity to speech. The arcuate fasciculus, a suggested marker of language in BPP, showed similar volume and integrity to a healthy control. The frontal aslant tract, linked to oromotor function, was partially reconstructed. These findings highlight the importance of assessing the auditory cortex beyond speech production structures to understand absent speech in BPP. Despite profound cortical alterations, the intrinsic motor network and motor-speech pathways remained largely intact. This case underscores the need for comprehensive phenotyping using multiple MRI modalities to uncover causes of severe disruption in language development.
Topics: Humans; Auditory Cortex; Speech; Polymicrogyria; Speech Perception; Magnetic Resonance Imaging; Phenotype; Abnormalities, Multiple; Intellectual Disability; Malformations of Cortical Development
PubMed: 38109835
DOI: 10.1016/j.cortex.2023.11.006 -
EClinicalMedicine Nov 2023Magnetic Resonance (MR) imaging is key for investigation of suspected newborn brain abnormalities. Access is limited in low-resource settings and challenging in infants...
BACKGROUND
Magnetic Resonance (MR) imaging is key for investigation of suspected newborn brain abnormalities. Access is limited in low-resource settings and challenging in infants needing intensive care. Portable ultralow field (ULF) MRI is showing promise in bedside adult brain imaging. Use in infants and children has been limited as brain-tissue composition differences necessitate sequence modification. The aim of this study was to develop neonatal-specific ULF structural sequences and test these across a range of gestational maturities and pathologies to inform future validation studies.
METHODS
Prospective cohort study within a UK neonatal specialist referral centre. Infants undergoing 3T MRI were recruited for paired ULF (64mT) portable MRI by convenience sampling from the neonatal unit and post-natal ward. Key inclusion criteria: 1) Infants with risk or suspicion of brain abnormality, or 2) preterm and term infants without suspicion of major genetic, chromosomal or neurological abnormality. Exclusions: presence of contra-indication for MR scanning. ULF sequence parameters were optimised for neonatal brain-tissues by iterative and explorative design. Neuroanatomic and pathologic features were compared by unblinded review, informing optimisation of subsequent sequence generations in a step-wise manner. Main outcome: visual identification of healthy and abnormal brain tissues/structures. ULF MR spectroscopy, diffusion, susceptibility weighted imaging, arteriography, and venography require pre-clinical technical development and have not been tested.
FINDINGS
Between September 23, 2021 and October 25, 2022, 102 paired scans were acquired in 87 infants; 1.17 paired scans per infant. Median age 9 days, median postmenstrual age 40 weeks (range: 31-53). Infants had a range of intensive care requirements. No adverse events observed. Optimised ULF sequences can visualise key neuroanatomy and brain abnormalities. In finalised neonatal sequences: T2w imaging distinguished grey and white matter (7/7 infants), ventricles (7/7), pituitary tissue (5/7), corpus callosum (7/7) and optic nerves (7/7). Signal congruence was seen within the posterior limb of the internal capsule in 10/11 infants on finalised T1w scans. In addition, brain abnormalities visualised on ULF optimised sequences have similar MR signal patterns to 3T imaging, including injury secondary to infarction (6/6 infants on T2w scans), hypoxia-ischaemia (abnormal signal in basal ganglia, thalami and white matter 2/2 infants on T2w scans, cortical highlighting 1/1 infant on T1w scan), and congenital malformations: polymicrogyria 3/3, absent corpus callosum 2/2, and vermian hypoplasia 3/3 infants on T2w scans. Sequences are susceptible to motion corruption, noise, and ULF artefact. Non-identified pathologies were small or subtle.
INTERPRETATION
On unblinded review, optimised portable MR can provide sufficient contrast, signal, and resolution for neuroanatomical identification and detection of a range of clinically important abnormalities. Blinded validation studies are now warranted.
FUNDING
The Bill and Melinda Gates Foundation, the MRC, the Wellcome/EPSRC Centre for Medical Engineering, the MRC Centre for Neurodevelopmental Disorders, and the National Institute for Health Research (NIHR) Biomedical Research Centres based at Guy's and St Thomas' and South London & Maudsley NHS Foundation Trusts and King's College London.
PubMed: 38106560
DOI: 10.1016/j.eclinm.2023.102253 -
Quantitative Imaging in Medicine and... Dec 2023The most common subtypes of malformations of cortical development (MCDs) are gray matter heterotopia (GMH), focal cortical dysplasia (FCD), and polymicrogyria (PMG)....
BACKGROUND
The most common subtypes of malformations of cortical development (MCDs) are gray matter heterotopia (GMH), focal cortical dysplasia (FCD), and polymicrogyria (PMG). This study aimed to characterize the possible neurometabolic abnormalities and heterogeneity in different MCDs subtypes using proton magnetic resonance spectroscopy (H-MRS).
METHODS
In this prospective cross-sectional study, we recruited 29 patients with MCDs and epilepsy, including ten with GMH, ten with FCD, and nine with PMG, as well as 25 age- and sex-matched healthy controls (HC) from the Epilepsy Center of West China Hospital of Sichuan University between August 2018 and November 2021. Inclusion criteria for the patients were based upon typical magnetic resonance imaging (MRI) findings of MCDs and full clinical assessment for epilepsy. Single-voxel point-resolved spectroscopy was used to acquire data from both the lesion and the normal-appearing contralateral side (NACS) in patients and from the frontal lobe in HC. Metabolite measures, including N-acetyl aspartate (NAA), myoinositol (Ins), choline (Cho), creatine (Cr), and glutamate + glutamine (Glx) concentrations, were quantitatively estimated with linear combination model (LCModel) software and corrected for the partial volume effect of cerebrospinal fluid (CSF).
RESULTS
The NAA concentration was lower and the Ins concentration was higher in the MCDs lesions than in the NACS and in HC (P=0.002-0.007), and the Cho and Cr concentrations were higher in MCDs lesions than in HC (P=0.001-0.016). Moreover, the Cho concentration was higher in NACS than in HC (P=0.015). In the GMH lesions, the only metabolic alteration was an NAA reduction (GMH_lesion HC: P=0.001). In the FCD lesions, there were more metabolite abnormalities than in the other two subtypes, particularly a lower NAA and a higher Ins than in HC and NACS (P=0.012-0.042). In the PMG lesions, Cr (lesion HC or NACS: P=0.017-0.021) and Glx (lesion NACS: P=0.043) were increased, while NAA was normal. Correlation analysis revealed that the Cr concentration in MCDs lesions was positively correlated with seizure frequency (r=0.411; P=0.027).
CONCLUSIONS
Based upon H-MRS, our study demonstrated that different MCDs subtypes exhibited variable metabolic features, which may be associated with distinct functional and cytoarchitectural properties.
PubMed: 38106257
DOI: 10.21037/qims-23-552 -
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 -
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 -
Epileptic Disorders : International... Apr 2024PACS2 pathogenic variants are associated with an autosomal dominant syndrome (OMIM DEE66), associating developmental and epileptic encephalopathy, facial dysmorphism,...
PACS2 pathogenic variants are associated with an autosomal dominant syndrome (OMIM DEE66), associating developmental and epileptic encephalopathy, facial dysmorphism, and cerebellar dysgenesis. However, no malformation of cortical development has been reported yet. We report here a seven-year-old child with a history of infantile epileptic spasm syndrome and a right insular polymicrogyria and pachygyria due to de novo PACS2 recurrent mutation c.625G>A (p.Glu209Lys). Our observation raises the question of the role of PACS2 in the cortical development. It also reminds the importance of cerebellar anomalies in the recognition of PACS-related DEE.
Topics: Child; Humans; Epilepsy; Epilepsy, Generalized; Mutation; Phenotype; Polymicrogyria; Syndrome; Vesicular Transport Proteins
PubMed: 38031819
DOI: 10.1002/epd2.20184 -
Fetal Diagnosis and Therapy 2024Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome is a rare autosomal dominant disorder characterized by megalencephaly (i.e., overgrowth of the...
INTRODUCTION
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome is a rare autosomal dominant disorder characterized by megalencephaly (i.e., overgrowth of the brain), polymicrogyria, focal hypoplasia of the cerebral cortex, and polydactyly. Persistent hyperplastic primary vitreous (PHPV) involves a spectrum of congenital ocular abnormalities that are characterized by the presence of a vascular membrane behind the lens.
CASE PRESENTATION
Here, we present a case of foetal MPPH with PHPV that was diagnosed using prenatal ultrasound. Ultrasound revealed the presence of megalencephaly, multiple cerebellar gyri, and hydrocephalus. Whole-exome sequencing confirmed the mutation of the AKT3 gene, which led to the consideration of MPPH syndrome. Moreover, an echogenic band with an irregular surface was observed between the lens and the posterior wall of the left eye; therefore, MPPH with PHPV was suspected.
CONCLUSION
MPPH syndrome with PHPV can be diagnosed prenatally.
Topics: Pregnancy; Female; Humans; Polymicrogyria; Persistent Hyperplastic Primary Vitreous; Magnetic Resonance Imaging; Malformations of Cortical Development; Hydrocephalus; Megalencephaly; Polydactyly; Syndrome; Ultrasonography, Prenatal
PubMed: 38008077
DOI: 10.1159/000535509 -
American Journal of Medical Genetics.... Apr 2024Bilateral perisylvian polymicrogyria (BPP) is a structural malformation of the cerebral cortex that can be caused by several genetic abnormalities. The most common...
Bilateral perisylvian polymicrogyria (BPP) is a structural malformation of the cerebral cortex that can be caused by several genetic abnormalities. The most common clinical manifestations of BPP include intellectual disability and epilepsy. Cytoplasmic FMRP-interacting protein 2 (CYFIP2) is a protein that interacts with the fragile X mental retardation protein (FMRP). CYFIP2 variants can cause various brain structural abnormalities with the most common clinical manifestations of intellectual disability, epileptic encephalopathy and dysmorphic features. We present a girl with multiple disabilities and BPP caused by a heterozygous, novel, likely pathogenic variant (c.1651G>C: p.(Val551Leu) in the CYFIP2 gene. Our case report broadens the spectrum of genetic diversity associated with BPP by incorporating CYFIP2.
Topics: Female; Humans; Intellectual Disability; Polymicrogyria; Abnormalities, Multiple; Malformations of Cortical Development; Brain Diseases; Adaptor Proteins, Signal Transducing
PubMed: 37975178
DOI: 10.1002/ajmg.a.63478