Brain Magnetic Resonance Imaging Abnormalities Research Articles

Brain Magnetic Resonance Imaging Findings in Patients with Developmental Delay in Addis Ababa, Ethiopia.

Developmental delay is a major health problem throughout the world causing significant individual disability. Even though physical examination and patient history are the most important and basic evaluations of patients with developmental delay, additional investigations are usually required in supporting or reaching a diagnosis among which is neuroimaging. This study aims to assess brain Magnetic resonance imaging (MRI) patterns in patients presented with developmental delay. A retrospective analysis of 164 patients who had undergone brain Magnetic Resonance Imaging (MRI) evaluation for the developmental delay was done. The study was conducted between March to November 2021 G.C at Tikur Anbessa Specialized Hospital (TASH). The patients' clinical history and magnetic resonance imaging reports were reviewed from their medical records. All patients with developmental delay who had brain MRI evaluation at TASH and at one private diagnostic center in Addis Ababa were included in the study. A total of 164 patients were included in this study of which 95(57.9%) were male and 69(42.1%) female patients were seen. A total of 120 patients (73.2%) showed abnormal brain MRI studies. Previous neurovascular insults were the most common abnormalities seen in 75(45.7%) patients followed by imaging findings of congenital and developmental abnormalities seen in 20(12.2%) patients. Brain MRI is an important input in the evaluation of patients with developmental delay. It can give evidence for the cause of developmental delay, especially in the diagnosis of perinatal/hypoxic-ischemic insults, and congenital and developmental malformations.

Central nervous system magnetic resonance imaging abnormalities and neurologic outcomes in pediatric patients with congenital nevi: A 10-year multi-institutional retrospective study

High-risk congenital melanocytic nevi (CMN) are associated with abnormalities of the central nervous system (CNS), prompting magnetic resonance imaging (MRI) screening guidelines. Describe MRI brain and spine abnormalities in children with CMN and report trends between nevus features, MRI findings, and neurologic outcomes. Retrospective review of individuals aged ≤18years with an MRI of the brain and/or spine and at least 1 dermatologist-diagnosed CMN. Three hundred fifty-two patients were identified. Forty-six children had CMN that prompted an MRI of the brain and/or spine (50% male, average age at first image, 354.8days). In these children, 8 (17%) had melanin detected in the CNS, of whom all had >4 CMN. One developed brain melanoma (fatal). In patients without CNS melanin, 4 had concerning imaging. Concerning MRI patients had more neurodevelopmental problems, seizures, neurosurgery, and death than individuals with unremarkable imaging. Three hundred six patients received MRIs for other reasons; none detected melanin. No children with only multiple small CMN (n=15) had concerning imaging. Lack of a control group, cohort size, and retrospective methods. MRI of the brain and spine is useful for detecting intervenable abnormalities in high-risk children. Healthy infants with few small CMN may not require screening MRI.

Clinical and Neurodevelopmental Characteristics of Enterovirus and Parechovirus Meningitis in Neonates.

BackgroundNon-polio-enteroviruses (EV) and human parechoviruses (HPeV) are small RNA viruses, which in newborns cause infections with a wide range of severity. Today molecular biology tools allow us to diagnose viral meningitis in neonates, sparing patients from useless antibiotics. Data on neurodevelopmental outcome of children who contract enterovirus meningitis in early childhood are still limited in the literature.AimsTo evaluate the neurodevelopmental outcome of newborns with documented enterovirus and parechovirus meningitis contracted within the first months of life.MethodsEnterovirus and parechovirus were detected on cerebrospinal fluid (CSF) and plasma by RT-PCR. The virological typing was done according to WHO recommendations. During the hospitalization each neonate underwent many diagnostic and instrumental examinations, to evaluate any neurological lesions attributable to the infection. After the discharge children entered in an outpatient interdisciplinary assessment process, comprehensive of the administration of Bayley III scales up to 12 months old.ResultsWe observed longitudinally 30 children, born at term (mean GA 39.7 ± 0.8 weeks, mean birthweight was 3,457 ± 405 grams), who contracted enterovirus and parechovirus meningitis within the first month of life (mean age at diagnosis was 15.8 ± 7.33 days). We were able to perform the genetic typing only on 15/30 (50.0%) cerebrospinal fluid (CSF) samples from 15 neonates. We found MRI anomalies in 9/26 observed neonates (34.6%): one of them presented brainstem abnormality that are specific of enteroviral central nervous system (CNS) involvement. During the follow up children displayed an overall normal neurodevelopment and no deficit in visual and hearing areas. The mean cognitive (105.19 ± 8.71), speech (100.23 ± 8.22) and motor (97.00 ± 8.98) composite scores, assessed by Bayley III, were normal in 29/30 (96.7%). Despite this, children with pathological brain magnetic resonance imaging (MRI) scored significantly lower (p = 0.01) than children with normal brain MRI on cognitive subscale at 12 months of life.ConclusionsEarly enterovirus infections can be associated to brain MRI abnormalities, more frequently the earlier the infection. Although within a normal range, our children with pathological brain MRI scored significantly lower than those with normal brain MRI on cognitive subscale at 12 months of life.

Clinical Neuroimaging Findings in Catatonia: Neuroradiological Reports of MRI Scans of Psychiatric Inpatients With and Without Catatonia.

Catatonia is a debilitating psychomotor disorder. Previous neuroimaging studies have used small samples with inconsistent results. The authors aimed to describe the structural neuroradiological abnormalities in clinical magnetic resonance imaging (MRI) brain scans of patients with catatonia, comparing them with scans of psychiatric inpatients without catatonia. They report the largest study of catatonia neuroimaging to date. In this retrospective case-control study, neuroradiological reports of psychiatric inpatients who had undergone MRI brain scans for clinical reasons were examined. Abnormalities were classified by lateralization, localization, and pathology. The primary analysis was prediction of catatonia by presence of an abnormal MRI scan, adjusted for age, sex, Black race-ethnicity, and psychiatric diagnosis. Scan reports from 79 patients with catatonia and 711 other psychiatric inpatients were obtained. Mean age was 36.4 (SD=17.3) for the cases and 44.5 (SD=19.9) for the comparison group. Radiological abnormalities were reported in 27 of 79 cases (34.2%) and in 338 of 711 in the comparison group (47.5%) (odds ratio [OR]=0.57, 95% confidence interval [CI]=0.35, 0.93; adjusted OR=1.11, 95% CI=0.58, 2.14). Among the cases, most abnormal scans had bilateral abnormalities (N=23, 29.1%) and involved the forebrain (N=25, 31.6%) and atrophy (N=17, 21.5%). Patients with catatonia were commonly reported to have brain MRI abnormalities, which largely consisted of diffuse cerebral atrophy rather than focal lesions. No evidence was found that these abnormalities were more common than in other psychiatric inpatients undergoing neuroimaging, after adjustment for demographic variables. Study limitations included a heterogeneous control group and selection bias in requesting scans.

Significance of Polyspikes on Electroencephalography in Children with Focal Epilepsy

Purpose: Epilepsy is one of the most common neurological disorders in both adults and children. After detailed history-taking, electroencephalography (EEG) is the most important investigation in the evaluation of epilepsy patients. Polyspikes, defined as a sequence of two or more spikes, are among the findings that can be seen on EEGs of epilepsy patients, but the literature on their significance in focal epilepsy patients is scarce. Therefore, in the current study, we investigated the significance of polyspikes on EEG in childhood focal epilepsy. Methods: A retrospective analysis was conducted of data from children who were diagnosed with focal epilepsy and received anti-seizure medications at Pusan National University Children’s Hospital. Results: Among the 1,125 children included in this study, 468 (41.6%) showed interictal polyspikes on their EEGs. In the multivariate analysis, only the presence of brain magnetic resonance imaging (MRI) abnormalities was significantly associated with the presence of interictal polyspikes on EEGs. Among patients with brain MRI abnormalities, localized polyspikes were significantly associated with focal cortical dysplasia, while multifocal polyspikes were significantly associated with perinatal insults (hypoxic-ischemic encephalopathy and destructive encephalomalacia). Conclusion: Focal epilepsy patients with interictal polyspikes were more likely to have a structural etiology. Furthermore, patients with localized polyspikes were more likely to have focal cortical dysplasia as the structural etiology, while patients with multifocal polyspikes were more likely to have perinatal insults as the structural etiology. This study demonstrates that focal polyspikes can be used as markers of the possible presence of a structural etiology in routine practice.

Clinicoradiologic Correlation in 22 Egyptian Children With Megalencephalic Leukoencephalopathy With Subcortical Cysts.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare genetic form of cerebral white matter disease whose clinicoradiologic correlation has not been completely understood. In this study, we investigated the association between clinical and brain magnetic resonance imaging (MRI) features in 22 Egyptian children (median age 7 years) with MLC. Gross motor function was assessed using the Gross Motor Function Classification System, and evaluation of brain MRI followed a consistent scoring system. Each parameter of extensive cerebral white matter T2 hyperintensity, moderate-to-severe wide ventricle/enlarged subarachnoid space, and greater than 2 temporal subcortical cysts was significantly associated (P < .05) with worse Gross Motor Function Classification System score, language abnormality, and ataxia. Having >2 parietal subcortical cysts was significantly related to a worse Gross Motor Function Classification System score (P = .04). The current study indicates that patients with MLC manifest signification association between certain brain MRI abnormalities and neurologic features, but this should be confirmed in larger studies.

Brain Magnetic Resonance Imaging Findings in Infantile Spasms.

Background: Infantile spasms are an age-specific epileptic disorder. They occur in infancy and early childhood. They can be caused by multiple etiologies. Structural abnormalities represent an important cause of infantile spasms. Brain magnetic resonance imaging (MRI) is one of the integral modalities in the evaluation of this condition. Purpose: The aim of this study is to review and analyze the clinical characteristics and brain MRI findings in a cohort of children diagnosed with infantile spasms. Material and Methods: A cohort of fifty-six children diagnosed with infantile spasms in infancy and early childhood was included. All of them underwent brain MRI for evaluation. The study was conducted in the period from January 2016 to January 2020. Results: Females comprised 57% of the cohort. The mean age for seizure onset was 5.9 months (SD 2.7). Forty-one patients (73%) had active epilepsy, and 51% were diagnosed with global developmental delay. Consanguinity was present in 59% of the cohort. Most of the follow-up MRIs showed structural abnormalities (84%). Hypoxia was reported in 17% of MRIs. Malformations of cortical development were seen in five patients. Brain MRI findings were normal in 16% of patients, and delayed myelination was seen in nineteen patients. Most of the children with active epilepsy (64%) and developmental delay (82%) had an abnormal brain MRI. It was noticed that abnormal second brain MRIs were more likely to be associated with active epilepsy and developmental delay (p = 0.05). Conclusions: Brain MRI is an integral part of infantile spasms’ clinical evaluation. Infantile spasms and abnormal brain MRI can be associated with active epilepsy and global developmental delay.

Brain Magnetic Resonance Imaging Classification Using Deep Learning Architectures with Gender and Age.

Usage of effective classification techniques on Magnetic Resonance Imaging (MRI) helps in the proper diagnosis of brain tumors. Previous studies have focused on the classification of normal (nontumorous) or abnormal (tumorous) brain MRIs using methods such as Support Vector Machine (SVM) and AlexNet. In this paper, deep learning architectures are used to classify brain MRI images into normal or abnormal. Gender and age are added as higher attributes for more accurate and meaningful classification. A deep learning Convolutional Neural Network (CNN)-based technique and a Deep Neural Network (DNN) are also proposed for effective classification. Other deep learning architectures such as LeNet, AlexNet, ResNet, and traditional approaches such as SVM are also implemented to analyze and compare the results. Age and gender biases are found to be more useful and play a key role in classification, and they can be considered essential factors in brain tumor analysis. It is also worth noting that, in most circumstances, the proposed technique outperforms both existing SVM and AlexNet. The overall accuracy obtained is 88% (LeNet Inspired Model) and 80% (CNN-DNN) compared to SVM (82%) and AlexNet (64%), with best accuracy of 100%, 92%, 92%, and 81%, respectively.

Radiological characteristics of neuromyelitis optica spectrum disorder in Egypt

AbstractBackgroundNeuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease of the central nervous system, which mainly affects the optic nerves and the spinal cord. Magnetic resonance imaging (MRI) plays an important role in the diagnosis of NMOSD based on the 2015 consensus criteria.MethodsThe objective of this study was to describe the MRI characteristics of NMOSD patients in Egypt. This were a prospective, observational study on patients fulfilling the 2015 diagnostic criteria of NMOSD. Patients were recruited consecutively from the Neurology, Psychiatry and Neurosurgery hospital, Assiut University Hospitals, Egypt from March 2019 until August 2020. Data on demographics, clinical and laboratory features were collected. MRI scan results were reviewed for each patient and compared according to Aquaporin4‐seropositivity.ResultsNinety patients fulfilled NMOSD diagnostic criteria. The mean age at onset was 30.7±11.8 with a female predominance of 3:1. AQP4 antibodies were positive in 77/90 patients (85.6%). Seventy‐two patients (80%) had acute myelitis, 44 cases (61.1%) had longitudinally extensive transverse myelitis (LETM) and 61 cases (87.1%) had a central position in the cord. Bright spotty lesions (BSL) were found in 44 cases (61.1%). The most common site of cord involvement was the cervical region. Abnormal MRI brain scans were found in 81.1% of patients. No statistically significant differences could be found between the two groups.ConclusionThere was a high frequency of abnormal spine and brain MRI findings in the Egyptian population. Even though no specific patterns were typical for AQP4‐specific serostatus, certain findings may suggest NMOSD diagnosis and warrant AQP4‐IgGs testing.

Sepsis-Related Brain MRI Abnormalities Are Associated With Mortality and Poor Neurological Outcome in Pediatric Sepsis

BackgroundIt is not known whether brain magnetic resonance imaging (MRI) abnormalities in pediatric sepsis are associated with clinical outcomes. Study objectives were to (1) determine the prevalence and type of sepsis-related neuroimaging abnormalities evident on clinically indicated brain MRI in children with sepsis and (2) test the association of these abnormalities with mortality, new disability, length of stay (LOS), and MRI indication. MethodsRetrospective cohort study of 140 pediatric patients with sepsis and a clinically indicated brain MRI obtained within 60 days of sepsis onset at a single, large academic pediatric intensive care unit (PICU). Two radiologists systematically reviewed the first post-sepsis brain MRI and determined which abnormalities were sepsis-related. Outcomes compared in patients with versus without sepsis-related MRI abnormalities. ResultsPICU mortality was 7%. Thirty patients had one or more sepsis-related MRI abnormality, yielding a prevalence of 21% (95% confidence interval 15%, 28%). Among those, 53% (16 of 30) had sepsis-related white matter signal abnormalities; 53% (16 of 30) sepsis-related ischemia, infarction, or thrombosis; and 27% (eight of 30) sepsis-related posterior reversible encephalopathy. Patients with one or more sepsis-related MRI abnormality had increased mortality (17% vs 5%; P = 0.04), new neurological disability at PICU discharge (32% vs 11%; P = 0.03), and longer PICU LOS (median 18 vs 11 days; P = 0.04) compared with patients without. ConclusionsIn children with sepsis and a clinically indicated brain MRI, 21% had a sepsis-related MRI abnormality. Sepsis-related MRI abnormalities were associated with increased mortality, new neurological disability, and longer PICU LOS.

The clinical features, treatment and outcomes of 33 children from Northwestern China with Anti-N-methyl-D-aspartate receptor encephalitis

ABSTRACT Objectives We analyzed the clinical features and outcomes of children with anti-N-methyl-D–aspartate receptor (anti-NMDAR) encephalitis in Northwestern China. Methods We retrospectively recruited 33 pediatric patients with anti-NMDAR encephalitis in Northwestern China from December 2013 to April 2020. The demographics, clinical features, treatments, and outcomes were reviewed. Results 33 patients with anti-NMDAR encephalitis were enrolled in this study (a median age of 6.8 years, 20 females and 13 males). The initial symptoms included seizures (42.4%), psychiatric symptoms (39.4%), speech dysfunction (12.1%), and paralysis (6.1%). During the course of the disease, 31 patients (93.9%) presented with psychiatric symptoms, 29 patients (87.9%) presented with speech dysfunction, 25 patients (75.8%) presented with movement disorders and 24 patients (72.7%) presented with sleep disorders followed by seizures, consciousness disturbance, autonomic nervous dysfunction, paralysis, and hypoventilation. 12 patients (36.4%) had abnormal cerebrospinal fluid (CSF) findings, 10 patients (30.3%) exhibited abnormal brain magnetic resonance imaging (MRI) results, and 29 patients (87.9%) showed abnormal Electroencephalography (EEG) findings. None of the patients had tumors. All patients received first-line immunotherapy and 8 patients both received first and second-line immunotherapy. 30 of the 33 patients achieved good outcomes (score on the modified Rankin Scale [mRS] of 0–2), whilst the other 3 patients had poor outcomes (mRS score of 3–6). Conclusions Patients with higher CSF anti-NMDAR body titer were more likely to develop sleep disorders, consciousness disturbances and more severe disease states.

Methotrexate(MTX) Induced Leukoencephalopathy(LE) and Relation of Vitamin B12, Folate and / or Homocysteine Levels with MTX Toxicity: A Prospective Study

▪Background: MTX-induced neurotoxicity is often associated with leukoencephalopathy, and the diagnostic radiological feature in magnetic resonance imaging (MRI) is white matter hyper intensities. The clinical significance of these white matter changes is unknown. The risk factors of MTX-induced acute leukoencephalopathy are not well established. Few authors have suggested increased homocysteine or alteration of Central Nervous System (CNS) folate, vitamin b12 homeostasis may be associated with CNS toxicity. It is a usual clinical practice to withhold methotrexate during further duration of chemotherapy after an episode of leukoencephalopathy but the risk of neurotoxicity must be weighed against the risk of relapse of leukemia. Moreover, there is limited data on continued treatment with High-dose methotrexate (HD-MTX) or Intrathecal Methotrexate (IT-MTX) or Oral-MTX in patients who developed leukoencephalopathy.Objective: The study aims to 1) identify the risk and prevalence of leukoencephalopathy in patients of Acute Lymphoblastic Leukemia (ALL) receiving intrathecal or high dose or oral methotrexate therapy through sequential MRI Brain study. 2) Safety of re-administration of methotrexate in patients with documented toxic leukoencephalopathy 3) The relationship of serum homocysteine, vitamin b12 and folate levels with methotrexate induced leukoencephalopathyMethods: Our study enrolled 34 newly diagnosed pediatric ALL / Lymphoblastic Lymphoma (LBL) patients (age ≤18 years) between June 2019 & June 2020. Induction chemotherapy was initiated as per modified ALL IC BFM 2002 protocol after obtaining informed consent. Apart from the Hematological investigations, Bone Marrow Aspiration and Biopsy, Flow Cytometry/Immunohistochemistry (IHC), Cytogenetics, Molecular study were done. All the patients underwent MRI Brain and Serum homocysteine, Vitamin B12, Folate level measurement (sequentially as per protocol at 4 different time points). 1st time point - AT DIAGNOSIS, i.e. before starting methotrexate, 2nd time point - POST CONSOLIDATION, 3rd time point - POST EXTRACOMPARTMENT THERAPY, 4th time point - IN MAINTENANCE, thus analyzing leukoencephalopathy secondary to different modes of administration of methotrexate therapy. At all-time points serum folate, vitamin b12 or homocysteine level were done before administering methotrexate and any association with development of leukoencephalopathy was analyzed.Results: We identified Leukoencephalopathy secondary to methotrexate in 6.03% (7/116) on MRI brain in 5 of 33 (15.15%) patients of which 1 (3.03%) had symptomatic LE and 4 (12.12%) were clinically asymptomatic. All our LE patients were in the age group more than or equal to 10 years. We found no increase in the incidence of leukoencephalopathy secondary to methotrexate: leucovorin ratio, also there was no difference in the incidence with respect to mode of administration of MTX (IT/HD/ORAL), even there was no increase in incidence after 4 courses of high dose methotrexate. MRI at baseline was not a predictor of development of leukoencephalopathy. 3 out of 5 patients with LE had abnormal b12/folate/homocysteine with corresponding abnormal MRI Brain at pre-specified time point. Also 4 patients with abnormal b12/folate/homocysteine levels had intractable cytopenias while on chemotherapy and more after HD MTX therapy which got corrected after supplementation with vitamin b12 and folic acid.Conclusion: MTX-induced clinical leukoencephalopathy is transient, and most patients can be re-challenged with subsequent MTX without recurrence of acute or subacute symptoms. MRI at baseline was not a predictor of development of leukoencephalopathy. More multi institutional prospective studies of large number of patients are needed to study the incidence of MTX-induced leukoencephalopathy and its relation with folic acid, vitamin b12 and homocysteine level. DisclosuresNo relevant conflicts of interest to declare.

De Novo Variants in the DYNC1H1 Gene Associated With Infantile Spasms.

Objective: The DYNC1H1 gene is related to a variety of diseases, including spinal muscular atrophy with lower extremity–predominant 1, Charcot–Marie–Tooth disease type 2O, and mental retardation, autosomal dominant13 (MRD13). Some patients with DYNC1H1 variant also had epilepsy. This study aimed to detect DYNC1H1 variants in Chinese patients with infantile spasms (ISs).Methods: We reviewed clinical information, video electroencephalogram (V-EEG), and neuroimaging of a newly identified cohort of five patients with de novo DYNC1H1gene variants.Results: Five patients with four DYNC1H1variants from four families were included. All patients had epileptic spasms (ESs), the median age at seizure onset was 7.5 months (range from 5 months to 2 years 7 months), and the interictal V-EEG results were hypsarrhythmia. Four of five patients had brain magnetic resonance imaging (MRI) abnormalities. Four de novo DYNC1H1 variants were identified, including two novel variants (p.N1117K, p.M3405L) and two reported variants (p.R1962C, p.F1093S). As for the variant site, two variants are located in the tail domain, one variant is located in the motor domain, and one variant is located in the stalk domain. All patients had tried more than five kinds of antiepileptic drugs. One patient has been controlled well by vigabatrin (VGB) for 4 years, and another patient by VGB and steroids for 1.5 years. The other three patients still had frequent ESs. All patients had severe intellectual disability and development delays.Significance: IS was one of the phenotypes of DYNC1H1 variants. Most patients had non-specific brain MRI abnormality. Two of four DYNC1H1 variants were novel, expanding the variant spectrum. The IS phenotype was related to the variant's domains of DYNC1H1 variant sites. All patients were drug-refractory and showed development delays.

Epidemiological and Clinical Characteristics of Sporadic Creutzfeldt-Jakob Disease: A Retrospective Study in Eastern China.

Objective: We aimed to characterize the epidemiological and clinical characteristics of sporadic Creutzfeldt–Jakob disease (sCJD) in eastern China in this retrospective study.Methods: This study enrolled 67 patients with sCJD hospitalized in a grade-A tertiary hospital in eastern China from January 2010 to January 2020. Demographic data, clinical symptoms, brain magnetic resonance imaging (MRI), electroencephalogram (EEG), cerebrospinal fluid (CSF) 14-3-3 protein test, polymerase chain reaction (PCR), and DNA sequence determination of genes were collected and analyzed.Results: There were 62 patients with probable sCJD and 5 patients with possible sCJD. Male (28 cases) to female (39 cases) ratio was 1:1.39. Mean age at disease onset was 64.42 ± 9.00 years (range: 29–88 years), and mean survival time was 9.39 ± 12.58 months (range: 1–60 months for patients who received the follow-ups). The most common onset symptoms were dementia (49.25%), movement disorder (44.78%), and visual disturbance (22.39%), while the most frequent clinical manifestations were language disorders (74.63%), ataxia (70.15%), and myoclonus (70.15%). The positive rates of brain MRI abnormalities, 14-3-3 protein in CSF, and periodic sharp wave complexes (PSWCs) on EEG were 84.90, 68.00, and 46.03%, respectively. The 14-3-3 protein positive (p = 0.033) and PSWCs on EEG (p = 0.020) acted as the favorable and unfavorable factor for over 1 year of survival time, respectively.Conclusions: There were some differences in epidemiological and clinical characteristics among patients in China and those of other countries. The prognosis and its influencing factors were relatively unexplored in China. The mean survival time of Chinese patients was longer than that of Caucasian patients but shorter than that of Japanese patients. The 14-3-3 protein in CSF and PSWCs on EEG were both closely related to the survival time. It is necessary to promote autopsy or biopsy to better understand sCJD in China.

Genotype and phenotype of children with DEPDC5 gene variants related epilepsy

Objective: To summarize the clinical characteristics and the features of electroencephalograph (EEG) of children with DEPDC5 gene variants related epilepsy. Methods: The clinical data, gene variation, EEG and head magnetic resonance image (MRI) of 20 epileptic children with DEPDC5 gene variants admitted to Department of Pediatrics, Peking University First Hospital from May 2017 to November 2020 were retrospectively analyzed. Results: Twenty patients with heterozygous DEPDC5 gene variants were enrolled, 8 of 20 patients were nonsense variants, 6 were missense variants, 3 were frame-shift variants, 2 were splicing variants, and 1 was large fragment deletion. Sixteen cases had hereditary variation and 4 had de novo variation. Fifteen of variations were novel. Nine were male, while 11 were female. Their latest follow-up age ranged from 10 months to 13 years and one month.The epilepsy onset age ranged from 3 hours to 11 years and 3 months, the median age was 10.5 months. Twelve (60%) patients had developmental delay. Nineteen patients had focal seizures, 7 had epileptic spasms, 1 had multiple seizure types including tonic, atypical absence, dystonic and myoclonic seizures. Epileptic form discharges were observed in 18 patients during the interictal phase, and 11 were focal discharges, 7 were multifocal discharges. Ten (50%) patients had abnormal brain MRI, including focal cortical dysplasia in 5 patients, undefined malformation of cortical development in 4 patients, hemimegalencephaly in 1 patient. Four patients were diagnosed as West syndrome and one patient was diagnosed as Lennox-Gastaut syndrome. Fourteen (70%) patients were diagnosed as drug-resistant epilepsy. Four patients became seizure-free by treatment with anti-epileptic drugs. Three children were treated with surgery, and 2 of them became seizure-free, 1 had more than 75% reduction in seizures. Conclusions: DEPDC5 gene variant epilepsy is inherited with incomplete penetrance and focal seizure is the major seizure type. However, epileptic spasms, generalized seizures can also be observed. Half of the patients brain malformations. Most of the patients are drug-resistant epilepsy. Patients with clear epileptogenic zones can be treated with surgery. Treatment-resistant patients are more likely to be complicated with developmental delay.

A single center experience with publicly funded clinical exome sequencing for neurodevelopmental disorders or multiple congenital anomalies

Exome sequencing (ES) is an important diagnostic tool for individuals with neurodevelopmental disorders (NDD) and/or multiple congenital anomalies (MCA). However, the cost of ES limits the test's accessibility for many patients. We evaluated the yield of publicly funded clinical ES, performed at a tertiary center in Israel, over a 3-year period (2018–2020). Probands presented with (1) moderate-to-profound global developmental delay (GDD)/intellectual disability (ID); or (2) mild GDD/ID with epilepsy or congenital anomaly; and/or (3) MCA. Subjects with normal chromosomal microarray analysis who met inclusion criteria were included, totaling 280 consecutive cases. Trio ES (proband and parents) was the default option. In 252 cases (90.0%), indication of NDD was noted. Most probands were males (62.9%), and their mean age at ES submission was 9.3 years (range 1 month to 51 years). Molecular diagnosis was reached in 109 probands (38.9%), mainly due to de novo variants (91/109, 83.5%). Disease-causing variants were identified in 92 genes, 15 of which were implicated in more than a single case. Male sex, families with multiple-affected members and premature birth were significantly associated with lower ES yield (p < 0.05). Other factors, including MCA and coexistence of epilepsy, autism spectrum disorder, microcephaly or abnormal brain magnetic resonance imaging findings, were not associated with the yield. To conclude, our findings support the utility of clinical ES in a real-world setting, as part of a publicly funded genetic workup for individuals with GDD/ID and/or MCA.

Clinical characteristics, disease course, and outcomes of paediatric patients with myelin oligodendrocyte glycoprotein-Ab associated disease: A retrospective clinical study

ObjectiveTo delineate the outcomes of paediatric patients with myelin oligodendrocyte glycoprotein antibody disease (MOGAD). MethodsWe retrospectively analyzed the clinical characteristics, treatment, and outcomes of 34 paediatric patients with MOGAD from July 2015 to January 2020. ResultsThe median age at disease onset was 75.5 months (range: 19–170 months). The female-to-male ratio was 1:1.1. The median follow-up duration was 34.5 months (range: 14–63 months). Acute disseminated encephalomyelitis (ADEM) was the most common initial phenotype (52.9%), followed by optic neuritis (ON) (20.6%). Children with ADEM were younger than those with ON (P = 0.045). Twenty-eight (82.4%) and 18 (56.3%) children had abnormal brain and spinal magnetic resonance imaging, respectively, during the first acute attack. MOG-abs titers in children with ON were statistically higher than those in children with ADEM (P = 0.04). Thirty–two children accepted glucocorticoid treatment, while 33 (97%) children demonstrated clinical improvement within 1 week, 21 children (61.8%) achieved clinical recovery within 1 month. Eight children (23.5%) suffered a relapse, the median interval between the initial attack and recurrence was 13 (range: 3–36) months. We detected neurological sequelae in seven (20.6%) children, with visual dysfunction being the most common sequela (85.7%). ConclusionADEM was the most common phenotype in both monophasic and relapsed paediatric MOGAD, followed by ON. Majority of pediatric MOGAD patients were highly responsive to glucocorticoid. Despite a benign prognosis in most patients, some patients endure neurological sequelae, mainly visual impairment. Patients with initial visual impairment should be carefully evaluated and administered individualized immunotherapy.

Seizures in myelin oligodendrocyte glycoprotein antibody-associated disorders and related immune factors

PurposeEpileptic seizures in myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorders (MOGAD) have been increasingly reported in the past two decades. However, the characteristics and possible mechanism largely remain unknown. This study aimed to investigate the clinical characteristics and immune mechanism of epileptic seizures in children with MOGAD. MethodsWe conducted a retrospective single-center case-control study from February 2019 to February 2021. Clinical characteristics and immune parameters of enrolled patients with seizures (n = 12) in MOGAD (n = 32), as compared with the antibody-negative (n = 13) and control (n = 23) groups were then analyzed. ResultsSeizures occurred in 24.5% (12/49, including cases that were not enrolled) of MOGAD. In this group, magnetic resonance imaging (MRI) abnormalities, especially unilateral cortical lesion and leptomeningeal enhancement, were more frequent in patients with seizures than in individuals without seizures (p < 0.05). Levels of thyroid peroxidase antibodies (TPOAb) in the seizure+/MOG+ group were significantly (p < 0.05) higher than those in the seizure-/MOG+ and control groups, whereas no significant differences as compared with the seizure+/MOG- group were observed. TPOAb level and brain MRI performance may be associated with disease course, since two cases with increased TPOAb and abnormal brain MRI were reported, after a second seizure attack occurred. ConclusionUnilateral cerebral cortical encephalitis and isolated seizures, especially in clusters and focal seizures, may be special phenotypes of seizures in MOG-AD. TPOAb may be associated with seizures in immune-related neurological diseases, but not a specific marker of MOGAD. Therefore, TPOAb may be considered but not strongly recommended to be monitored in MOGAD.

Etiological Factors in Pediatric Pseudotumor Cerebri Cases

Objective: Pseudotumor cerebri (PTC) is the presence of the signs and symptoms of intracranial pressure increase in the absence of a tumoral, structural or vascular mass-occupying lesion. This study aimed to investigate the etiological factors involved in childhood PTC cases.Methods: Data of the patients presented to the Private Medical Park Samsun Hospital, pediatric neurology outpatient clinic with the preliminary diagnosis of PTC between June 2015 and December 2020 were retrospectively reviewed. Demographic data, presentation symptoms, neuro-ophthalmological examination findings, laboratory data, and radiological imaging (brain magnetic resonance imaging, magnetic resonance venography) findings. The female (i.e., Group 1) and male (i.e., Group 2) children were compared concerning the etiological factors.Results: The study cohort included 45 patients. There were 24 patients in Group 1 (i.e., female children) and 21 patients in Group 2 (i.e., male children). Among the 45 patients, 41 (91.1%) had an overt etiological factor. Mean age of the study patients were 9.06 year [2,5 months-18 years]. The most common symptom was headache (64.4%). Two groups were similar concerning mean patient age, pubertal stage, and rates of vitamin B12 deficiency, iron deficiency anemia, vitamin D deficiency, abnormal brain magnetic resonance imaging, and magnetic resonance venography findings. However, the obesity rate was significantly higher in Group 2 than Group 1 (32,7% vs. 12,5%, p&amp;lt;0.05). Conclusion: A thorough investigation concerning etiology is crucial in pediatric PTC cases regardless of patient gender. Timely investigations regarding etiology will lead to timely treatment of this clinical condition and prevent irreversible devastating complications such as permanent hearing loss.

A systematic review of brain MRI findings in monogenic disorders strongly associated with autism spectrum disorder

Research on monogenic forms of autism spectrum disorder (autism) can inform our understanding of genetic contributions to the autism phenotype; yet, there is much to be learned about the pathways from gene to brain structure to behavior. This systematic review summarizes and evaluates research on brain magnetic resonance imaging (MRI) findings in monogenic conditions that have strong association with autism. This will improve understanding of the impact of genetic variability on brain structure and related behavioral traits in autism. The search strategy for this systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias (ROB) assessment was completed on included studies using the Newcastle-Ottawa Scales. Of 4,287 studies screened, 69 were included pertaining to 13 of the top 20 genes with the strongest association with autism. The greatest number of studies related to individuals with PTEN variants and autism. Brain MRI abnormalities were reported for 12 of the 13 genes studied, and in 51.7% of participants across all 13 genes, including 100% of participants with ARID1B variants. Specific MRI findings were highly variable, with no clear patterns emerging within or between the 13 genes, although white matter abnormalities were the most common. Few studies reported specific details about methods for acquisition and processing of brain MRI, and descriptors for brain abnormalities were variable. ROB assessment indicated high ROB for all studies, largely due to small sample sizes and lack of comparison groups. Brain abnormalities are common in this population of individuals, in particular, children; however, a range of different brain abnormalities were reported within and between genes. Directions for future neuroimaging research in monogenic autism are suggested.