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Background: Congenital anomalies of the kidney and urinary tract (CAKUT) represent 20–30% of all birth defects and are often associated with extra-renal malformations. We investigated the frequency of brain/spine malformations and neurological features in children with CAKUT. Methods: We reviewed the clinico-radiological and genetic data of 199 out of 1,165 children with CAKUT evaluated from 2006 to 2023 (99 males, mean age at MRI 6.4 years) who underwent brain and/or spine MRI. Patients were grouped according to the type of CAKUT (CAKUT-K involving the kidney and CAKUT-H involving the inferior urinary tract). Group comparisons were performed using χ2 and Fisher exact tests. Results: Brain/spine malformations were observed in 101/199 subjects (50.7%), 8.6% (101/1165) of our CAKUT population, including midbrain-hindbrain anomalies (40/158, 25.3%), commissural malformations (36/158, 22.7%), malformation of cortical development (23/158, 14.5%), Chiari I anomaly (12/199, 6%), cranio-cervical junction malformations (12/199, 6%), vertebral defects (46/94, 48.9%), caudal regression syndrome (29/94, 30.8%), and other spinal dysraphisms (13/94, 13.8%). Brain/spine malformations were more frequent in the CAKUT-K group (62.4%, p < 0.001). Sixty-two subjects (62/199, 31.2%) had developmental delay/intellectual disability. Neurological examination was abnormal in 40/199 (20.1%). Seizures and/or electroencephalographic anomalies were reported in 28/199 (14%) and behavior problems in 19/199 subjects (9%). Developmental delay/intellectual disability was more frequent in kidney dysplasia (65.2%) and agenesis (40.7%) (p = 0.001). Conclusions: We report a relative high frequency of brain/spine malformations and neurodevelopmental disorders in children with CAKUT who underwent MRI examinations in a tertiary referral center, widening the spectrum of anomalies associated with this condition. [ABSTRACT FROM AUTHOR]

Abusive head trauma (AHT) is a significant cause of morbidity and mortality for infants. Determining when to pursue a complete physical abuse evaluation can be difficult, especially for nonspecific findings or when a child appears clinically well. This retrospective study of 7 cases sought to describe the presentation, evaluation, and diagnoses for infants with abnormal subdural collections identified on cranial ultrasound for macrocephaly, and to determine how frequently AHT is diagnosed. The results of this study showed that while each patient presented due to asymptomatic macrocephaly, the extent of the workup varied greatly. In addition, no infants had suspicious injuries for abuse during the initial evaluation or the year following. In summary, among the 7 patients seen for asymptomatic macrocephaly with possible subdural hemorrhage, there were very inconsistent child abuse workups. There needs to be a standardized clinical guideline for this specific patient population involving a child abuse pediatric evaluation. [ABSTRACT FROM AUTHOR]

The article describes the case of a six-year-old girl with schizencephaly, shunted hydrocephalus, epilepsy, global development delay, diabetes insipidus, and spastic quadriplegic cerebral palsy. Topics discussed include findings on her medical examination, major categories of the differential diagnosis for a child with acquired chest wall mass, and final diagnosis of thoraco-abdominal actinomycosis with chest wall invasion.

The pathological mechanism of autism spectrum disorder (ASD) remains unclear. Nowadays, surface-based morphometry (SBM) based on structural magnetic resonance imaging (sMRI) techniques have reported cortical thickness (CT) variations in ASD. However, the findings were inconsistent and heterogeneous. This current meta-analysis conducted a whole-brain vertex-wise coordinate‐based meta‐analysis (CBMA) on CT studies to explore the most noticeable and robust CT changes in ASD individuals by applying the seed-based d mapping (SDM) program. A total of 26 investigations comprised 27 datasets were included, containing 1,635 subjects with ASD and 1470 HC, along with 94 coordinates. Individuals with ASD exhibited significantly altered CT in several regions compared to HC, including four clusters with thicker CT in the right superior temporal gyrus (STG.R), the left middle temporal gyrus (MTG.L), the left anterior cingulate/paracingulate gyri, the right superior frontal gyrus (SFG.R, medial orbital parts), as well as three clusters with cortical thinning including the left parahippocampal gyrus (PHG.L), the right precentral gyrus (PCG.R) and the left middle frontal gyrus (MFG.L). Adults with ASD only demonstrated CT thinning in the right parahippocampal gyrus (PHG.R), revealed by subgroup meta-analyses. Meta-regression analyses found that CT in STG.R was positively correlated with age. Meanwhile, CT in MFG.L and PHG.L had negative correlations with the age of ASD individuals. These results suggested a complicated and atypical cortical development trajectory in ASD, and would provide a deeper understanding of the neural mechanism underlying the cortical morphology in ASD. [ABSTRACT FROM AUTHOR]

Over time, fetal MR neuro-imaging has undergone continuous improvement; presently, it plays a pivotal role in the diagnosis of an expanding array of complex neurological conditions. Within this pictorial essay, our focus will be exclusively directed towards those cutting-edge clinical applications, which currently yield valuable diagnostic insights on a single case basis. Specifically, the pictorial examples will center on some abnormal entities and their features at an earlier fetal stage. [ABSTRACT FROM AUTHOR]

Background: Prenatal alcohol exposure (PAE) is associated with abnormalities in cortical structure and maturation, including cortical thickness (CT), cortical volume, and surface area. This study provides a longitudinal context for the developmental trajectory and timing of abnormal cortical maturation in PAE. Methods: We studied 35 children with PAE and 30 nonexposed typically developing children (Comparisons), aged 8–17 at enrollment, who were recruited from the University of Minnesota FASD Program. Participants were matched on age and sex. They underwent a formal evaluation of growth and dysmorphic facial features associated with PAE and completed cognitive testing. MRI data were collected on a Siemens Prisma 3T scanner. Two sessions, each including MRI scans and cognitive testing, were spaced approximately 15 months apart on average. Change in CT and performance on tests of executive function (EF) were examined. Results: Significant age‐by‐group (PAE vs. Comparison) linear interaction effects in CT were observed in the parietal, temporal, occipital, and insular cortices suggesting altered developmental trajectories in the PAE vs. Comparison groups. Results suggest a pattern of delayed cortical thinning in PAE, with the Comparison group showing more rapid thinning at younger ages and those with PAE showing accelerated thinning at older ages. Overall, children in the PAE group showed reduced cortical thinning across time relative to the Comparison participants. Symmetrized percent change (SPC) in CT in several regions was significantly correlated with EF performance at 15‐month follow‐up for the Comparison group but not the group with PAE. Conclusions: Regional differences were seen longitudinally in the trajectory and timing of CT change in children with PAE, suggesting delayed cortical maturation and an atypical pattern of development compared with typically developing individuals. In addition, exploratory correlation analyses of SPC and EF performance suggest the presence of atypical brain–behavior relationships in PAE. The findings highlight the potential role of altered developmental timing of cortical maturation in contributing to long‐term functional impairment in PAE. [ABSTRACT FROM AUTHOR]

There may be distinct conduct disorder (CD) etiologies and neural morphologies in adolescents with high callous unemotional (CU) traits versus low CU traits. Here, we employed surface-based morphometry methods to investigate morphological differences in adolescents diagnosed with CD [42 with high CU traits (CD-HCU) and 40 with low CU traits (CD-LCU)] and healthy controls (HCs, N = 115) in China. Whole-brain analyses revealed significantly increased cortical surface area (SA) in the left inferior temporal cortex and the right precuneus, but decreased SA in the left superior temporal cortex in the CD-LCU group, compared with the HC group. There were no significant cortical SA differences between the CD-HCU and the HC groups. Compared to the CD-HCU group, the CD-LCU group had a greater cortical thickness (CT) in the left rostral middle frontal cortex. Region-of-interest analyses revealed significant group differences in the right hippocampus, with CD-HCU group having lower right hippocampal volumes than HCs. We did not detect significant group differences in the amygdalar volume, however, the right amygdalar volume was found to be a significant moderator of the correlation between CU traits and the proactive aggression in CD patients. The present results suggested that the manifestations of CD differ between those with high CU traits versus low CU traits, and underscore the importance of sample characteristics in understanding the neural substrates of CD. [ABSTRACT FROM AUTHOR]

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]

Objective: Pediatric seizure is a condition that occurs due to many different underlying causes and causes fear and anxiety in families. In our study, it was aimed to evaluate pediatric seizure cases who applied to our hospital. Methods: Patients aged 0-18 years, who applied to the pediatric emergency department of our hospital between May 2018 and May 2020, were retrospectively analyzed. The patients were evaluated in terms of age, gender, seizure types, familial genetic predisposition, examination, treatment and follow-up. Seizures were divided into 2 groups as focal and generalized according to the International League Against Epilepsy (ILAE) 2017 classification. The treatment methods applied with cranial magnetic resonance imaging and electroencephalography recordings of the patients were evaluated. Results: Of the 118 patients included in the study, 70 (59%) were girls and 48 (41%) were boys. The mean age was 60 (3-192) months. Family history was present in 18 (15%) cases. 8 (7%) of the seizures are partial and 110 (93%) of them are generalized. Since seizure recurrence was observed within 24 hours in 5 of 36 patients who were evaluated as febrile seizures, they were evaluated as complicated febrile seizures and drug treatment was started. The other 31 patients were evaluated as simple febrile seizures. There was no biochemical abnormality in the seizure etiology in any of the cases. Cranial magnetic resonance imaging revealed polymicrogyria in 2 patients, hydrocephalus in 2 patients, brain tumor in 1 patient, and arteriovenous malformation in 1 patient. Conclusions: In cases presenting with seizures, the underlying causes should be identified and their treatment should be arranged. Cases with recurrent seizures should also be followed closely. [ABSTRACT FROM AUTHOR]

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]

Background: Surface ictal electroencephalographic (EEG) monitoring has an important role in the presurgical evaluation of patients with focal cortical dysplasia (FCD). This study aimed to examine the characteristics of seizure onset pattern (SOP) on surface ictal EEG. This information will be useful for invasive monitoring planning.Methods: We reviewed 290 seizures from 31 patients with intractable seizures related to FCD type II (6 patients with FCD IIa and 25 patients with FCD IIb). We categorized the SOPs into five patterns and evaluated the relationships between the SOPs and the location and pathology of the FCD II subtype.Results: The most common SOP was no apparent change (39.0%), followed by rhythmic slow wave and repetitive spikes/sharp waves. The SOP of rhythmic slow wave was associated with FCD II in the temporal lobe (P < 0.001), and the SOP of no apparent change was associated with FCD II in the occipital lobe (P = 0.012). The SOPs of rhythmic slow waves and fast activity were most common in FCD IIa, P < 0.001 and 0.031, respectively. The repetitive spikes/sharp waves SOP was the most common pattern in FCD IIb (P < 0.001). The surface SOPs provided correct localization and lateralization of epileptic foci in FCD in 62.1% and 62.7%, respectively. In 61.3% of the patients, over 50% of the SOPs in each patient indicated accurate localization.Conclusions: SOPs in surface EEG monitoring are beneficial for presurgical evaluation and lead to localization of epileptic foci and pathologic subtypes of FCD. [ABSTRACT FROM AUTHOR]

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]

The study aimed to investigate the clinical implications and natural history of primary intraparenchymal lesions in patients with neurofibromatosis type 2. Radiological findings of 15 neurofibromatosis type 2 cases were retrospectively collected. Twenty-seven primary intraparenchymal lesions were observed in 7 out of 15 patients (47%). Cortical/subcortical T2 hyperintense lesions and enlarged Virchow–Robin spaces were the most common findings in five and four patients, respectively. During the follow-up period (median 84 months), one new primary intraparenchymal lesion was identified and increased lesions were observed in two cases on contrast-enhanced MRI. Surgical resection was performed in one case pathologically diagnosed with atypical meningioma. Twenty-five other lesions without contrast enhancement presented no apparent growth during follow-up. Although most primary intraparenchymal lesions are benign, a subset of cases would present newly developed or increased lesions on contrast-enhanced MRI. Careful monitoring is necessary for such cases, and pathological confirmation should be considered. [ABSTRACT FROM AUTHOR]

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]

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]

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]

Purpose: To figure out the spectra features of malformations of cortical development (MCDs) and the differences between MCDs subcategories. Methods: Twenty patients and 18 controls were studied. The patients included two subcategories: disorders of migration (DOM) and postmigration (DOPM). Spectra of patients were acquired from both the lesion and the normal-appearing contralateral side (NACS), and they were compared to those of the controls obtained from the frontal lobe. Results: Compared to the controls, a decreased NAA (P = 0.002) was identified in MCDs. After dividing the MCDs into the DOM and DOPM, we found that NAA reduction was only notable in the DOM (P = 0.007). Moreover, Ins and Cr of the DOPM were higher than those of the controls (P = 0.017 and 0.013) and the DOM (P = 0.027 and 0.001). Compared to the NACS, a decreased NAA (P = 0.042) and an increased Ins (P = 0.039) were identified in the lesion of MCDs. After dividing the MCDs into the DOM and DOPM, we found no significant differences in the DOM, but Ins, Cr, and Glx of the lesion were higher than those of the NACS (P = 0.007, 0.005 and 0.047) in the DOPM. In addition, we found that Cr and Glx correlated positively to the seizure frequency (P = 0.003 and 0.016). Conclusion: Decreased NAA was the prominent abnormality confirmed in MCDs. Spectra of different MCDs subcategories were different: the DOM was characterized by decreased NAA, while the DOPM was characterized by increased Ins. [ABSTRACT FROM AUTHOR]

Background: GLI3 encodes a zinc finger transcription factor that plays a role in the sonic hedgehog pathway. Germline pathogenic GLI3 variants are associated with Greig cephalopolysyndactyly and Pallister-Hall syndromes, two syndromes involving brain malformation and polydactyly.Methods: We identified patients with pathogenic GLI3 variants and brain malformations in the absence of polydactyly or other skeletal malformation.Results: Two patients were identified. Patient #1 is a 4-year-old boy with hypotonia and global developmental delay. Brain MRI showed a focal cortical dysplasia, but he had no history of seizures. Genetic testing identified a de novo likely pathogenic GLI3 variant: c.4453A>T, p.Asn1485Tyr. Patient #2 is a 4-year-old boy with hypotonia, macrocephaly, and global developmental delay. His brain MRI showed partial agenesis of the corpus callosum, dilatation of the right lateral ventricle, and absent hippocampal commissure. Genetic testing identified a de novo pathogenic GLI3 variant: c.4236_4237del, p.Gln1414AspfsTer21. Neither patient had polydactyly or any apparent skeletal abnormality.Conclusions: These patients widen the spectrum of clinical features that may be associated with GLI3 pathogenic variants to include hypotonia, focal cortical dysplasia, and other brain malformations, in the absence of apparent skeletal malformation. Further study is needed to determine if GLI3 pathogenic variants are a more common cause of focal cortical dysplasia or corpus callosum agenesis than presently recognized. [ABSTRACT FROM AUTHOR]

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]

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]

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]

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]

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]

Purpose: Recent research in epilepsy patients confirms our understanding of epilepsy as a network disorder with widespread cortical compromise. Here, we aimed to investigate the neocortical laminar architecture in patients with focal cortical dysplasia (FCD) and periventricular nodular heterotopia (PNH) using clinically feasible 3 T MRI. Methods: Eighteen epilepsy patients (FCD and PNH groups; n = 9 each) and age-matched healthy controls (n = 9) underwent T1 relaxation 3 T MRI, from which component probability T1 maps were utilized to extract sub-voxel composition of 6 T1 cortical layers. Seventy-eight cortical areas of the automated anatomical labeling atlas were divided into 1000 equal-volume sub-areas for better detection of cortical abnormalities, and logistic regressions were performed to compare FCD/PNH patients with healthy controls with the T1 layers composing each sub-area as regressors. Statistical significance (p < 0.05) was determined by a likelihood-ratio test with correction for false discovery rate using Benjamini-Hochberg method. Results: Widespread cortical abnormalities were observed in the patient groups. Out of 1000 sub-areas, 291 and 256 bilateral hemispheric cortical sub-areas were found to predict FCD and PNH, respectively. For each of these sub-areas, we were able to identify the T1 layer, which contributed the most to the prediction. Conclusion: Our results reveal widespread cortical abnormalities in epilepsy patients with FCD and PNH, which may have a role in epileptogenesis, and likely related to recent studies showing widespread structural (e.g., cortical thinning) and diffusion abnormalities in various human epilepsy populations. Our study provides quantitative information of cortical laminar architecture in epilepsy patients that can be further targeted for study in functional and neuropathological studies. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the gross white matter abnormalities in the structural brain MR imaging as well as white matter microstructural alterations using tract-based spatial statistics (TBSS) analysis of diffusion tensor imaging (DTI) in both affected and contralateral cerebral hemispheres of children with hemimegalencephaly (HMEG). Methods: From 2003 to 2019, we retrospectively reviewed brain MR images in 20 children (11 boys, 2 days–16.5 years) with HMEG, focusing on gross white matter abnormalities. DTI was evaluated in 12 patients (8 boys, 3 months–16.5 years) with HMEG and 12 age-, sex-, and magnetic field strength-matched control subjects. TBSS analysis was performed to analyze main white matter tracts. Regions of significant differences in fractional anisotropy (FA) were determined between HMEG and control subjects and between affected and contralateral hemispheres of HMEG. Results: Gross white matter abnormalities were noted in both affected (n = 20, 100%) and contralateral hemisphere (n = 4, 20%) of HMEG. FA values were significantly decreased in both hemispheres of HMEG, compared with control subjects (P < 0.05). Contralateral hemispheres of HMEG showed regions with significantly decreased FA values compared with affected hemispheres (P < 0.05). Conclusions: In addition to gross white matter abnormalities particularly evident in affected hemispheres, DTI analysis detected widespread microstructural alterations in both affected and contralateral hemispheres in HMEG suggesting HMEG may involve broader abnormalities in neuronal networks. [ABSTRACT FROM AUTHOR]

Introduction. We surveyed nonretired American Academy of Pediatrics–member US pediatricians regarding common neurosurgical conditions, identifying specific areas of focus in education. Methods. Data were acquired via self-administered electronic questionnaire. Results. Of 505 total respondents, 56% reported neurology was not a required residency rotation, and 86% had diagnosed craniosynostosis, plagiocephaly, or macrocephaly. Craniosynostosis can mostly be diagnosed by physical examination alone, but almost 50% reported relying on skull X-rays. Fifty-four percent reported diagnosing ocular surface disease (OSD; with 15% to 40% not screening an infant despite well-established cutaneous markers). Seventy-four screened OSD in a patient with sacral dimple. Ninety-seven percent reported treating concussion, but nearly 25% did not manage these patients alone. Two out of 3 patients indicated head injury as most important for continuing education. Conclusion. Improved education for craniosynostosis, OSD, head injury, and concussion management are important for earlier diagnosis, management, and referral of some disorders, while decreasing resource utilization in others. These results should be used when considering pediatrician educational programs. [ABSTRACT FROM AUTHOR]

Background: Using text reports to communicate bilateral, symmetric, and zonal cortical brain atrophy in children with term hypoxic ischemic injury (HII) to parents and legal professionals contesting compensation rights can be difficult. Using standard cross-sectional images for explaining bilateral, regional brain imaging to laypeople is also challenging. A single flattened image of the brain surface, much like a map of the earth is derived from a globe, can be generated from curved reconstruction of magnetic resonance imaging (MRI) scans, i.e., a Mercator map. Laypeople's ability to identify abnormal "Mercator brain maps," without prior training, requires evaluation before use in nonmedical settings. Aim: To determine the sensitivity and specificity of laypeople in detecting abnormal pediatric Mercator flat-earth maps of the brain, without prior training. Methods and Materials: 10 Mercator brain maps were provided to 111 participants individually. The maps comprised 5 HII, 1 cortical dysplasia, and 4 normal cases. Participants were required to identify the abnormal scans. Sensitivity and specificity overall and for participants' subgroups were calculated. Results: Overall sensitivity and specificity were 67% and 80%, respectively. General radiologists (n = 12) had sensitivity and specificity of 91.2% and 94.6%, respectively. Laypeople (n = 54) had a sensitivity of 67% and specificity of 80%. Conclusion: The high specificity and sensitivity of radiologists validated the technique for distinguishing abnormal scans, regarding cortical pathology. High specificity of laypeople for identifying abnormal brains using Mercator maps indicates that this is a viable communication tool for demonstrating cortical MRI abnormalities of HII in children to laypersons. [ABSTRACT FROM AUTHOR]

Objective: To define the predictive value (PV) of known prognostic factors of fetal infection with Cytomegalovirus following maternal primary infection <14 weeks of gestation, at different time points of pregnancy: the end of the second trimester; following prenatal magnetic resonance imaging (MRI) at 32 weeks of gestation; and using all ultrasound scans performed in the third trimester (US3rdT).Design: A retrospective study.Setting: Reference fetal medicine unit.Population: Sixty-two fetuses infected <14 weeks of gestation.Methods: We defined second-trimester assessment (STA) as the combination of ultrasound findings <28 weeks of gestation and fetal platelet count at cordocentesis. Three groups were defined: normal, extracerebral, and cerebral STA.Main Outcome Measures: For each group, the PV of STA alone, STA + MRI, and STA + US3rdT were assessed retrospectively. Outcome at birth and at follow-up were reported.Results: The STA was normal, and with extracerebral and cerebral features, in 43.5, 42.0, and 14.5%, respectively. The negative PV of normal STA and MRI for moderate to severe sequelae was 100%. The residual risk was unilateral hearing loss in 16.7% of cases. Of pregnancies with cerebral STA, 44% were terminated. Following extracerebral STA, 48% of neonates were symptomatic and 30% had moderate to severe sequelae. In those cases, the positive and negative PV of MRI for sequelae were 33 and 73%, respectively. STA + US3rdT had a lower negative PV than MRI for symptoms at birth and for moderate to severe sequelae. Any false-positive findings at MRI were mostly the result of hypersignals of white matter.Conclusions: Serial assessment in the second and third trimesters by ultrasound and MRI is necessary to predict the risk of sequelae occurring in 35% of pregnancies following fetal infection in the first trimester of pregnancy.Tweetable Abstract: Serial ultrasound prognostic assessment following fetal CMV infection in the 1st trimester is improved by MRI at 32 weeks. [ABSTRACT FROM AUTHOR]

Background: Fetal alcohol spectrum disorders (FASD) describe a range of physical, behavioral, and cognitive impairments stemming from prenatal alcohol exposure (PAE). Although case studies have demonstrated striking visible brain abnormalities in humans (enlargement of the lateral ventricles, thinning or absence of the corpus callosum, etc.), few studies have systematically determined how these radiological findings generalize to the wider population of individuals living with FASD. Methods: This study examines rates of structural brain anomalies on magnetic resonance imaging (MRI) as determined by 2 radiologists in a retrospective blinded review of 163 controls and 164 individuals with PAE who were previously scanned as participants of past research studies. Incidental findings were categorized as normal variants, nonclinically significant incidental findings, or clinically significant incidental findings. Rates were compared between diagnostic subgroups using chi‐square analysis. Results: There was no significant difference in the overall rate of incidental findings between groups: 75% of controls and 73% of PAE participants had no incidental findings of any kind, and only 1% of controls and 3% of PAE participants had incidental finding of clinical significance (the remaining findings were considered nonsignificant anomalies or normal variants). When the PAE group was split by diagnosis, low‐lying cerebellar tonsils, polymicrogyria, and ventricular asymmetry/enlargement were all most prevalent in subjects with fetal alcohol syndrome/partial fetal alcohol syndrome. In addition, the overall rate of incidental findings was higher (41%) in participants with FAS/pFAS, compared to 25% in controls. No participants in this relatively large sample had corpus callosum agenesis. Conclusions: Although advanced quantitative MRI research has uncovered a range of differences in brain structure associated with FASD, this qualitative radiological study suggests that routine clinical MRI does not reveal a consistent pattern of brain abnormalities that can be used diagnostically in this population. [ABSTRACT FROM AUTHOR]

Background: Malformations of cortical development comprise phenotypically heterogeneous conditions, and the diagnostic value of genetic testing in blood still remains to be elucidated. We used targeted gene sequencing to identify malformations of cortical development caused by germline mutations and characteristics associated with pathogenic mutations.Methods: A total of 81 patients with malformations of cortical development were included. Genomic DNA was isolated from peripheral blood. Ninety-six genes were assessed using a targeted next-generation sequencing panel. Single-nucleotide variants and exonic and chromosomal copy number variations were examined with our customized pipeline.Results: Genetic causes were identified from blood in 19 (23.5%) patients with malformations of cortical development; 14 patients had pathogenic or likely pathogenic single-nucleotide variants in seven genes, including DCX (n = 5), DEPDC5 (n = 2), PAFAH1B1 (n = 3), TUBA1A (n = 1), TUBA8 (n = 1), TUBB2B (n = 1), and TUBB3 (n = 1). Five patients had pathogenic copy number variations. Multifocal involvement of the lesion (tangential distribution, P < 0.001) and concurrent involvement of multiple structures such as the cortex, white matter, and ventricle (radial distribution, P = 0.003) were more commonly found in patients with identified genetic causes. Intellectual disability was also more commonly associated with pathogenic mutations (P = 0.048). In a multivariable regression analysis, both tangential and radial radiological distribution of malformations of cortical development were independently associated with positive germline test results.Conclusion: We identified germline mutations in almost one-fourth of our patients with malformations of cortical development by using targeted gene sequencing. Germline abnormalities were more likely found in patients who had multifocal malformations of cortical development. [ABSTRACT FROM AUTHOR]

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]

Paradoxical cortical potential polarity of the upper extremity somatosensory evoked potential (SSEP) has been reported in cases of polymicrogyria (PMG) syndrome. To date, the pathophysiological basis of this electrophysiological aberration remains under investigation. Here we present a case of mild PMG that showed "layered" microgyri in the left frontoparietal cortices affecting both hand and foot sensorimotor areas. The SSEP recordings revealed an isolated polarity reversal of N20 from the dysplastic cortex. We postulate a central sulcus misfolding theory to explain the "positive" N20 potential recorded in the PMG cortex. [ABSTRACT FROM AUTHOR]

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]

• Subjects at ultra-high risk of psychosis (UHR) showed increased radial diffusivity in the left anterior thalamic radiation. • Reduced bilateral cortical thickness across the frontal, temporal and parietal cortices were found in UHR patients. • No correlations between white and grey matter abnormalities were identified in UHR subjects. There is increasing evidence of white matter (WM) and grey matter pathology in subjects at ultra-high risk of psychosis (UHR), although a limited number of diffusion-weighted magnetic resonance imaging (DW-MRI) and surface-based morphometry (SBM) studies have revealed anatomically inconsistent results. The present multimodal study applies tractography and SBM to analyze WM microstructure, whole-brain cortical anatomy, and potential interconnections between WM and grey matter abnormalities in UHR subjects. Thirty young male UHR patients and 30 healthy controls underwent DW-MRI and T1-weighted MRI. Fractional anisotropy; mean, radial, and axial diffusivity in 18 WM tracts; and vertex-based cortical thickness, area, and volume were analyzed. We found increased radial diffusivity in the left anterior thalamic radiation and reduced bilateral thickness across the frontal, temporal, and parietal cortices. No correlations between WM and grey matter abnormalities were identified. These results provide further evidence that WM microstructure abnormalities and cortical anatomical changes occur in the UHR state. Disruption of structural connectivity in the prefrontal-subcortical circuitry, likely caused by myelin pathology, and cortical thickness reduction affecting the networks presumably involved in processing and coordination of external and internal information streams may underlie the widespread deficits in neurocognitive and social functioning that are consistently reported in UHR subjects. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to review the clinical, neuroradiological and electroencephalographic (EEG) findings of patients with epilepsy and malformation of cortical development (MCD). Methods: A retrospective analysis of the medical records of epilepsy outpatients was done. Patients with epilepsy, MCD, and ≥18 years of age were included and classified according to the Barkovich classification (BC). Results: The files of 2027 patients were assessed, and 17 out of 1395 epilepsy patients who were followed-up were found to have MCD. The mean age was 26.5 years. Ten patients were male and 7 were female. The mean time of seizure onset was 13 years. In terms of seizure type, 11 patients had focal, 10 had generalized tonic-clonic, 1 had absence, 1 had tonic-atonic, and 1 had myoclonic. MRI showed 7 patients with cortical dysplasia, 4 with heterotopia, 2 with periventricular nodular heterotopia, 2 with schiezencephaly, 2 with lissencephaly, 1 with agyria, 1 with pachygyria, 1 with macrogyria, 1 with polymicrogyria, and 1 with tuberous sclerosis. EEG revealed focal epileptiform discharges in 5 patients, high-frequency activity in 2, generalized epileptiform discharge in 1, diffuse disorganized background activity in 1, and focal disorganized background activity in 1. EEG was normal in 7 patients. Four of them were on monotherapy and 13 on polytherapy. Conclusion: The MCDs classified in group 1 and 2 according to BC are more frequent. Treatment-resistant or good responsive cases can be seen and seizures can begin at any age. We concluded that the prevalence of MCD is 1.21%. The spectrum of epilepsy seen is extensive and the most common type of MCD is focal cortical dysplasia. [ABSTRACT FROM AUTHOR]

Background Cerebral cavernous malformations (CCMs) are vascular malformations that account for 5%–15% of all central nervous system vascular malformations. However, multiple CCMs, which can be sporadic or familial, are rare, with a prevalence of 0.1%–0.5%. Case Description Here, we presented a rare case of sporadic multiple CCMs in an infant, which were accompanied with multiple cavernous malformations of the chest and skin. Conclusions CCMs were pathologically diagnosed through the total resection of the pineal regional lesion. We also observed a spontaneous regression of the remaining lesions during a follow-up period of 2 years. To our knowledge, this is the first case of CCMs in an infant in the English-language literature. Highlights • We present a rare case of sporadic multiple CCMs in an infant accompanied by multiple CMs of the chest and skin. • The condition can be diagnosed on characteristic imaging or by pathologic changes. • Spontaneous regression of the remaining lesions was observed during a follow-up period of 2 years. • To our best knowledge, the case we presented is the first report to date. [ABSTRACT FROM AUTHOR]

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]

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]

Background The aim of this study is to investigate the utility of 3-Tesla MRI in cases of partial onset epilepsy with a previous normal CT scan. We confer the results of MRI findings in 50 cases of partial onset epilepsy from 2014–16 using 3-Tesla MRI. Materials and methods Study was conducted on 50 patients of partial onset epilepsy from April 2014 to March 2016 from a tertiary health centre in Rajasthan, India using 3-Tesla Philips Ingenia scanner. All patients of partial epilepsy having a normal CT scan were included and underwent MRI brain with epilepsy protocol. Patients with isolated generalized, myoclonic or absence seizure types were excluded. Those having inflammatory or granulomatous lesions on MRI were excluded from the analysis. Results There were a total of 50 patients (28 males), mean age of onset was 20.21 years, ranging from 7 to 50 years; commonest presentation was that of focal seizures combined with multiple seizure types (60%). Out of these patients, MRI could localize a structural lesion in 64% cases who were having no corresponding abnormalities on a CT scan with a sensitivity of 86.7% and specificity of 73.5%. The detected abnormalities were Mesial temporal sclerosis in 30% (n = 15), Vascular malformation 10% (n = 5), Cortical malformation 8% (n = 4), Encephalitis 8% (n = 4), Neurodegenerative 4% (n = 8), cerebritis 2% (n = 1) and paraganglioma 2% (1). Conclusion In evaluation of structural lesions in cases of partial onset epilepsy, 3-Tesla MRI should be a prerequisite. Detection of focal structural lesion may help in planning epilepsy surgery for some of these candidates in future. [ABSTRACT FROM AUTHOR]

Abstract Background Neurodegenerative diseases involving protein aggregation often accompany psychiatric symptoms. Frontotemporal lobar degeneration (FTLD) associated with TAR DNA-binding protein 43 (TDP-43) aggregation is characterized by progressive neuronal atrophy in frontal and temporal lobes of cerebral cortex. Furthermore, patients with FTLD display mental dysfunction in multiple behavioral dimensions. Nevertheless, their molecular origin for psychiatric symptoms remains unclear. Methods In FTLD neurons and mouse models with TDP-43 aggregates, we examined coaggregation between TDP-43 and disrupted in schizophrenia 1 (DISC1), a key player in the pathology of mental conditions and its effects on local translation in dendrites and psychiatric behaviors. The protein coaggregation and the expression level of synaptic proteins were also investigated with postmortem brains from patients with FTLD (n = 6). Results We found cytosolic TDP-43/DISC1 coaggregates in brains of both FTLD mouse model and patients with FTLD. At the mechanistic levels, the TDP-43/DISC1 coaggregates disrupted the activity-dependent dendritic local translation through impairment of translation initiation and, in turn, reduced synaptic protein expression. Behavioral deficits detected in FTLD model mice were ameliorated by exogenous DISC1 expression. Conclusions Our findings reveal a novel role of the aggregate-prone TDP-43/DISC1 protein complex in regulating local translation, which affects aberrant behaviors relevant to multiple psychiatric dimensions. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We aimed to evaluate the long-term outcome of resective epilepsy surgery in patients with Lennox-Gastaut syndrome (LGS). METHODS: We reviewed the case reports of 90 patients with LGS who had undergone resective surgery between 2003 and 2014 at the Severance Children's Hospital and managed them for a minimum period of 2 years. RESULTS: At the time of surgery, the patients were between 3.0 and 23.5 years old (mean ± SD: 9.3 ± 4.4). The time from seizure onset to surgery ranged from 0.7 to 20.1 years (7.2 ± 4.3). On postoperative follow-up for an average period of 6.1 ± 2.2 years (range: 2.1--11.4 years), 45 patients (50.0%) had no seizures, and 15 (16.7%) reported infrequent seizures. Seizure-free outcomes were achieved in 15 of the 21 (71.4%) hemispherectomies, 23 of the 51 (45.1%) multilobar resections, and 7 of the 18 (38.9%) single lobar resections. On high-resolution MRIs, 20 patients (22.2%) had negative findings, 8 of whom (40.0%) became seizure-free after resective surgery. Malformation of cortical development was the most common pathologic finding and was noted in 57 patients (63.3%). Seizure-free patients achieved better adaptive behavior and social competence than did patients with persistent seizures at the second (2--3 years after surgery) and third (4--6 years after surgery) follow-ups, as indicated by social quotients (P < .05). CONCLUSIONS: Resective surgery is a viable option in some patients to treat seizures that are associated with LGS, with a high probability of seizure control and better adaptive function. [ABSTRACT FROM AUTHOR]

BACKGROUND: Sleep disturbance plays a significant role in cognitive impairment following traumatic brain injury (TBI). OBJECTIVES: To summarize recent findings that examine sleep disturbance and cognition in TBI. METHODS: Epidemiological information on sleep disorders in people with TBI is presented. A simple introduction to the role of sleep in normal cognition provides context for the literature on clinical populations. Current theory on the mechanisms underlying cognitive problems in people with sleep disorder is briefly described. Findings on the relationship between sleep disorder and cognitive problems in TBI is examined in more detail. RESULTS: Consistent reports of an association between sleep duration and cognition include several studies noting positive associations (shorter sleep duration accompanies cognitive impairment) and others observing negative associations (longer sleep duration accompanies cognitive problems). Both insomnia and hypersomnolence are forms of sleep disturbance that disrupt key mental processes such as memory consolidation. Obstructive sleep apnea, cerebral structural abnormalities, neurochemical changes and psychiatric pathology are implicated. CONCLUSIONS: Additional information is needed on how severity of injury impacts sleep and cognition. Hypothesized mechanisms underlying the effects of sleep on cognition in TBI should be empirically tested. Further, discrepancies between objective and subjective measures of sleep and cognition must be explored. [ABSTRACT FROM AUTHOR]

The Sip1 mutation plays the main role in pathogenesis of the Mowat-Wilson syndrome, which is characterized by the pronounced epileptic symptoms. Cortical neurons of homozygous mice with Sip1 mutation are resistant to AMPA receptor activators. Disturbances of the excitatory signaling components are also observed on such a phenomenon of neuroplasticity as hypoxic preconditioning. In this work, the mechanisms of loss of the AMPA receptor's ability to precondition by episodes of short-term hypoxia were investigated on cortical neurons derived from the Sip1 homozygous mice. The preconditioning effect was estimated by the level of suppression of the AMPA receptors activity with hypoxia episodes. Using fluorescence microscopy, we have shown that cortical neurons from the Sip1 fl/fl mice are characterized by the absence of hypoxic preconditioning effect, whereas the amplitude of Ca 2+ -responses to the application of the AMPA receptor agonist, 5-Fluorowillardiine, in neurons from the Sip1 mice brainstem is suppressed by brief episodes of hypoxia. The mechanism responsible for this process is hypoxia-induced desensitization of the AMPA receptors, which is absent in the cortex neurons possessing the Sip1 mutation. However, the appearance of preconditioning in these neurons can be induced by phosphoinositide-3-kinase activation with a selective activator or an anti-inflammatory cytokine interleukin-10. [ABSTRACT FROM AUTHOR]

Purpose: In this paper, I will report the range of appearances of schizencephaly in children and fetuses by reviewing a 10-year experience from a single centre and detail classification systems for the different forms of schizencephaly. This will lead to re-assessment of possible aetiological and mechanistic causes of schizencephaly.Methods: All cases of pediatric and fetal schizencephaly were located on the local database between 2007 and 2016 inclusive. The studies were reviewed for the presence, location and type of schizencephaly, as well as the state of the (cavum) septum pellucidum, the location of the fornices and the presence of other brain abnormalities.Results: The review included 21 children and 11 fetuses with schizencephaly. Schizencephaly (type 1) was found in 9% of children but no fetuses, schizencephaly (type 2) was present in 67% of the pediatric cases and in 45% of fetuses, whilst schizencephaly (type 3) was present in approximately 24% of children and 55% of fetuses. Other brain abnormalities were found in 67% of children and 55% of fetuses.Conclusion: I have proposed a new system for classifying schizencephaly that takes into account all definitions of the abnormality in the literature. Using that approach, I have described the appearances and associations of pediatric and fetal cases of schizencephaly from a single centre. Review of the current literature appears to favour an acquired destructive aetiology for most cases of schizencephaly, and I have proposed a mechanism to explain the cortical formation abnormalities found consistently in and around areas of schizencephaly. [ABSTRACT FROM AUTHOR]

OBJECTIVES: We assessed the adherence to neuroimaging guidelines and the diagnostically relevant yield of neuroimaging in newly presenting early life epilepsy (ELE). METHODS: There were 775 children with a new diagnosis of epilepsy (<3 years old at onset) who were recruited through the ELE study at 17 US pediatric epilepsy centers (2012-2015) and managed prospectively for 1 year. The data were analyzed to assess the proportion of children who underwent neuroimaging, the type of neuroimaging, and abnormalities. RESULTS: Of 725 children (93.5%) with neuroimaging, 714 had an MRI (87% with seizure protocols) and 11 had computed tomography or ultrasound only. Etiologically relevant abnormalities were present in 290 individuals (40%) and included: an acquired injury in 97 (13.4%), malformations of cortical development in 56 (7.7%), and other diffuse disorders of brain development in 51 (7.0%). Neuroimaging was abnormal in 160 of 262 (61%) children with abnormal development at diagnosis versus 113 of 463 (24%) children with typical development. Neuroimaging abnormalities were most common in association with focal seizure semiology (40%), spasms (47%), or unclear semiology (42%). In children without spasms or focal semiology with typical development, 29 of 185 (16%) had imaging abnormalities. Pathogenic genetic variants were identified in 53 of 121 (44%) children with abnormal neuroimaging in whom genetic testing was performed. CONCLUSIONS: Structural abnormalities occur commonly in ELE, and adherence to neuroimaging guidelines is high at US pediatric epilepsy centers. These data support the universal adoption of imaging guidelines because the yield is substantially high, even in the lowest risk group. [ABSTRACT FROM AUTHOR]

Focal cortical dysplasia (FCD) is the most commonly encountered developmental malformation that causes refractory epilepsy. Focal cortical dysplasia type 2 is one of the most usual neuropathological findings in tissues resected therapeutically from patients with drug-resistant epilepsy. Unlike other types of FCD, it is characterized by laminar disorganization and dysplastic neurons, which compromise the organization of the six histologically known layers in the cortex; the morphology and/or cell location can also be altered. A comprehensive review about the pathogenesis of this disease is important because of the necessity to update the results reported over the past years. Here, we present an updated review through Pubmed about the mammalian target of rapamycin (MTOR) pathway in FCD type 2. A wide variety of aspects was covered in 44 articles related to molecular and cellular biology, including experiments in animal and human models. The first publications appeared in 2004, but there is still a lack of studies specifically for one type of FCD. With the advancement of techniques and greater access to molecular and cellular experiments, such as induced pluripotent stem cells (iPSCs) and organoids, it is believed that the trend is increasing the number of publications contributing to the achievement of new discoveries. [ABSTRACT FROM AUTHOR]

The article presents a case study of Japanese boy who presented with ventricular enlargement at 28-week gestational age was born at gestational age 38 weeks and 2 days. It mentions that he also presented with forehead protrusion, sacral cusp depression, low auricle, depressed nasal bridge and postaxial polydactyly, but no somatic asymmetry.