OBJECTIVE: We comprehensively characterized a large pediatric cohort with focal cortical dysplasia (FCD) type 1 to expand the phenotypic spectrum and to identify predictors of postsurgical outcomes. METHODS: We included pediatric patients with histopathological diagnosis of isolated FCD type 1 and at least 1 year of postsurgical follow-up. We systematically reanalyzed clinical, electrophysiological, and radiological features. The results of this reanalysis served as independent variables for subsequent statistical analyses of outcome predictors. RESULTS: All children (N = 31) had drug-resistant epilepsy with varying impacts on neurodevelopment and cognition (presurgical intelligence quotient [IQ]/developmental quotient scores = 32-106). Low presurgical IQ was associated with abnormal slow background electroencephalographic (EEG) activity and disrupted sleep architecture. Scalp EEG showed predominantly multiregional and often bilateral epileptiform activity. Advanced epilepsy magnetic resonance imaging (MRI) protocols identified FCD-specific features in 74.2% of patients (23/31), 17 of whom were initially evaluated as MRI-negative. In six of eight MRI-negative cases, fluorodeoxyglucose-positron emission tomography (PET) and subtraction ictal single photon emission computed tomography coregistered to MRI helped localize the dysplastic cortex. Sixteen patients (51.6%) underwent invasive EEG. By the last follow-up (median = 5 years, interquartile range = 3.3-9 years), seizure freedom was achieved in 71% of patients (22/31), including seven of eight MRI-negative patients. Antiseizure medications were reduced in 21 patients, with complete withdrawal in six. Seizure outcome was predicted by a combination of the following descriptors: age at epilepsy onset, epilepsy duration, long-term invasive EEG, and specific MRI and PET findings. SIGNIFICANCE: This study highlights the broad phenotypic spectrum of FCD type 1, which spans far beyond the narrow descriptions of previous studies. The applied multilayered presurgical approach helped localize the epileptogenic zone in many previously nonlesional cases, resulting in improved postsurgical seizure outcomes, which are more favorable than previously reported for FCD type 1 patients.
- MeSH
- Child MeSH
- Electroencephalography * methods MeSH
- Epilepsy MeSH
- Focal Cortical Dysplasia MeSH
- Cohort Studies MeSH
- Infant MeSH
- Humans MeSH
- Magnetic Resonance Imaging * MeSH
- Malformations of Cortical Development, Group I * surgery complications diagnostic imaging MeSH
- Malformations of Cortical Development surgery complications diagnostic imaging MeSH
- Adolescent MeSH
- Positron-Emission Tomography MeSH
- Child, Preschool MeSH
- Drug Resistant Epilepsy * surgery diagnostic imaging physiopathology MeSH
- Treatment Outcome MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Although neuromelanin-sensitive magnetic resonance imaging (NM-MRI) has been used to evaluate early neurodegeneration in Parkinson's disease, studies concentrating on the locus coeruleus (LC) in pre-dementia stages of dementia with Lewy bodies (DLB) are lacking. OBJECTIVES: The aims were to evaluate NM-MRI signal changes in the LC in patients with mild cognitive impairment with Lewy bodies (MCI-LB) compared to healthy controls (HC) and to identify the cognitive correlates of the changes. We also aimed to test the hypothesis of a caudal-rostral α-synuclein pathology spread using NM-MRI of the different LC subparts. METHODS: A total of 38 MCI-LB patients and 59 HCs underwent clinical and cognitive testing and NM-MRI of the LC. We calculated the contrast ratio of NM-MRI signal (LC-CR) in the whole LC as well as in its caudal, middle, and rostral MRI slices, and we compared the LC-CR values between the MCI-LB and HC groups. Linear regression analyses were performed to assess the relationship between the LC-CR and cognitive outcomes. RESULTS: The MCI-LB group exhibited a significant reduction in the right LC-CR compared to HCs (P = 0.021). The right LC-CR decrease was associated with impaired visuospatial memory in the MCI-LB group. Only the caudal part of the LC exhibited significant LC-CR decreases in MCI-LB patients compared to HCs on both sides (P < 0.0001). CONCLUSIONS: This is the first study that focuses on LC-CRs in MCI-LB patients and analyzes the LC subparts, offering new insights into the LC integrity alterations in the initial stages of DLB and their clinical correlates. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
- MeSH
- alpha-Synuclein metabolism MeSH
- Lewy Body Disease * diagnostic imaging pathology MeSH
- Cognitive Dysfunction * diagnostic imaging pathology physiopathology etiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Locus Coeruleus * diagnostic imaging pathology MeSH
- Magnetic Resonance Imaging * MeSH
- Neuropsychological Tests MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Spatial navigation deficits are early symptoms of Alzheimer's disease (AD). The apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for AD. This study investigated effects of APOE genotype on spatial navigation in biomarker-defined individuals with amnestic mild cognitive impairment (aMCI) and associations of AD biomarkers and atrophy of AD-related brain regions with spatial navigation. METHODS: 107 participants, cognitively normal older adults (CN, n = 48) and aMCI individuals stratified into AD aMCI (n = 28) and non-AD aMCI (n = 31) groups, underwent cognitive assessment, brain MRI, and spatial navigation assessment using the Virtual Supermarket Test with egocentric and allocentric tasks and a self-report questionnaire. Cerebrospinal fluid (CSF) biomarkers (amyloid-β1-42, phosphorylated tau181 and total tau) and amyloid PET imaging were assessed in aMCI participants. RESULTS: AD aMCI participants had the highest prevalence of APOE ε4 carriers and worst allocentric navigation. CSF levels of AD biomarkers and atrophy in AD-related brain regions were associated with worse allocentric navigation. Between-group differences in spatial navigation and associations with AD biomarkers and regional brain atrophy were not influenced by APOE genotype. Self-reported navigation ability was similar across groups and unrelated to spatial navigation performance. CONCLUSIONS: These findings suggest that allocentric navigation deficits in aMCI individuals are predominantly driven by AD pathology, independent of APOE genotype. This highlights the role of AD pathology as measured by biomarkers, rather than genetic status, as a major factor in navigational impairment in aMCI, and emphasizes the assessment of spatial navigation as a valuable tool for early detection of AD.
- MeSH
- Alzheimer Disease * genetics cerebrospinal fluid diagnostic imaging complications physiopathology pathology MeSH
- Amyloid beta-Peptides cerebrospinal fluid MeSH
- Apolipoprotein E4 * genetics MeSH
- Apolipoproteins E * genetics MeSH
- Atrophy MeSH
- Biomarkers cerebrospinal fluid MeSH
- Genotype MeSH
- Cognitive Dysfunction * genetics cerebrospinal fluid diagnostic imaging physiopathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Brain pathology diagnostic imaging MeSH
- Neuropsychological Tests MeSH
- Peptide Fragments cerebrospinal fluid MeSH
- Positron-Emission Tomography MeSH
- Spatial Navigation * physiology MeSH
- tau Proteins cerebrospinal fluid MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Current diagnostic methods for dyslexia primarily rely on traditional paper-and-pencil tasks. Advanced technological approaches, including eye-tracking and artificial intelligence (AI), offer enhanced diagnostic capabilities. In this paper, we bridge the gap between scientific and diagnostic concepts by proposing a novel dyslexia detection method, called INSIGHT, which combines a visualisation phase and a neural network-based classification phase. The first phase involves transforming eye-tracking fixation data into 2D visualisations called Fix-images, which clearly depict reading difficulties. The second phase utilises the ResNet18 convolutional neural network for classifying these images. The INSIGHT method was tested on 35 child participants (13 dyslexic and 22 control readers) using three text-reading tasks, achieving a highest accuracy of 86.65%. Additionally, we cross-tested the method on an independent dataset of Danish readers, confirming the robustness and generalizability of our approach with a notable accuracy of 86.11%. This innovative approach not only provides detailed insight into eye movement patterns when reading but also offers a robust framework for the early and accurate diagnosis of dyslexia, supporting the potential for more personalised and effective interventions.
- MeSH
- Reading MeSH
- Child MeSH
- Dyslexia * physiopathology diagnosis classification MeSH
- Humans MeSH
- Neural Networks, Computer * MeSH
- Fixation, Ocular * physiology MeSH
- Eye Movements physiology MeSH
- Eye-Tracking Technology * MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Previous research has demonstrated impaired proprioception and poorer responses to tactile deep pressure, visual-tactile integration, and vestibular stimuli in individuals with generalized hypermobility, potentially leading to sensory processing issues. Therefore, we aimed to explore the influence of hypermobility on somatognosia and stereognosia. METHODS: Forty-six participants were assessed using the Beighton score and categorized into three groups: non-hypermobile (n = 20), symptomatic hypermobile (n = 13), and asymptomatic hypermobile (n = 13). Somatognosia was evaluated using the shoulder width test in the vertical plane and pelvic width test in the vertical and horizontal planes. Stereognosia was assessed with Petrie's test. Spearman's rank correlation coefficient was examined the relationship between the Beighton score and measures of somatognosia and stereognosia. An unpaired t-test was used to compare variables between hypermobile (both symptomatic and asymptomatic) and non-hypermobile individuals, while a one-way ANOVA was used to compare data between the three groups. RESULTS: No significant relationship was observed between Beighton scores and measures of somatognosia and stereognosia. The t-test revealed no statistically significant differences between hypermobile and non-hypermobile groups in the shoulder width, two pelvic widths, and Petrie's tests (all p ≥ 0.105). Similarly, one-way ANOVA showed no statistically significant differences between the three groups across these tests (all p ≥ 0.177). CONCLUSIONS: The results indicate that somatognosia and stereognosia are not significantly related to the Beighton score and do not significantly differ between the groups studied. These sensory processing functions are unlikely to contribute to the common complaints reported by hypermobile individuals. CLINICAL TRIAL NUMBER: Not applicable.
- MeSH
- Agnosia * diagnosis MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Joint Instability * diagnosis physiopathology psychology complications epidemiology MeSH
- Proprioception physiology MeSH
- Stereognosis * physiology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
OBJECTIVE: Standard resective treatment of mesial temporal lobe epilepsy (MTLE) includes anteromesial temporal resection or amygdalohippocampectomy. One potential risk of these surgeries, especially in patients with magnetic resonance imaging (MRI)-negative findings, is postoperative memory impairment. An alternative to resective procedures that aim to preserve the neuropsychological profile are multiple hippocampal transections (MHTs). The objective of transections is to interrupt the longitudinal pathways of the hippocampus to prevent the spread of epileptic seizures while preserving the memory circuits. Previously performed MHT procedures were guided by questionable intraoperative electrocorticography. At our institution, we have developed and tested a modified technique to achieve complete MHTs. METHODS: Patients with pharmacoresistant unilaterally lateralized MTLE and MRI-negative findings with high risk of neuropsychologic deterioration were indicated for complete MHT. Comprehensive neuropsychological and epileptological evaluations and MRI follow-ups were conducted 1 year and 2 years postoperatively. The primary evaluated parameters were seizure reduction and significant changes in neuropsychological performance (± 1 SD). RESULTS: Complete MHTs were performed on 3 patients who completed 2-year follow-up. Two MHTs were performed on the right and 1 on the left side. Two patients are classified as Engel 1 and one patient as Engel 3. Two years after surgery, neuropsychologic evaluation did not show significant decrease in memory performance and performance in majority of cognitive tests. One-year MRI follow-up showed decrease of volume of hippocampus in all 3 patients. CONCLUSIONS: This modified technique of MHT in patients with MTLE and MRI-negative findings led to seizure reduction while preserving their neuropsychologic performance.
- MeSH
- Adult MeSH
- Epilepsy, Temporal Lobe * surgery diagnostic imaging MeSH
- Hippocampus * surgery diagnostic imaging MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Young Adult MeSH
- Follow-Up Studies MeSH
- Neurosurgical Procedures * methods MeSH
- Neuropsychological Tests MeSH
- Drug Resistant Epilepsy * surgery diagnostic imaging MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Offspring of parents with severe mental illness are at increased risk of developing psychopathology. Identifying endophenotypic markers in high-familial-risk individuals can aid in early detection and inform development of prevention strategies. Using generalized additive mixed models, we compared age trajectories of gyrification index (GI) and sulcal morphometric measures (i.e., sulcal depth, length and width) between individuals at familial risk for bipolar disorder or schizophrenia and controls. 300 T1-weighted MRI scans were obtained of 187 individuals (53 % female, age range: 8-23 years) at familial risk for bipolar disorder (n = 80, n families=55) or schizophrenia (n = 53, n families=36) and controls (n = 54, n families=33). 113 individuals underwent two scans. Globally, GI, sulcal depth and sulcal length decreased significantly with age, and sulcal width increased significantly with age in a (near-)linear manner. There were no differences between groups in age trajectories or mean values of gyrification or any of the sulcal measures. These findings suggest that, on average, young individuals at familial risk for bipolar disorder or schizophrenia have preserved developmental patterns of gyrification and sulcal morphometrics during childhood and adolescence.
- MeSH
- Bipolar Disorder * pathology MeSH
- Child MeSH
- Adult MeSH
- Genetic Predisposition to Disease MeSH
- Humans MeSH
- Magnetic Resonance Imaging * MeSH
- Adolescent MeSH
- Young Adult MeSH
- Cerebral Cortex growth & development diagnostic imaging pathology anatomy & histology MeSH
- Schizophrenia * pathology diagnostic imaging genetics MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Súhrn Detská chirurgia je lekárska špecializácia, ktorá sa zameriava na diagnostiku, liečbu a pooperačnú starostlivosť o deti s vrodenými a získanými anomáliami a chorobami. Cieľom detských chirurgov je zabezpečiť, aby deti dostali najlepšiu možnú starostlivosť a aby sa minimalizovali riziká a komplikácie spojené s chirurgickými zákrokmi. Súčasní detskí chirurgovia čelia mnohým výzvam, vrátane malému počtu detí s vrodenými vývojovými chybami; ekonomické tlaky a snaha o zvýšenie efektivity vedú k znižovaniu času stráveného na jednotlivých operáciách, čo môže obmedzovať možnosť dôkladného tréningu mladých chirurgov. Tieto výzvy vyžadujú inovatívne prístupy a neustále zlepšovanie vzdelávacích a tréningových metód. Minimálne invazívna chirurgia sa stala významnou súčasťou detskej chirurgie, prinášajúc benefity ako rýchlejšie zotavenie, menšie operačné rany a nižšie riziko infekcie. Avšak, minimálne invazívna detská chirurgia je technicky náročná a vyžaduje excelentnú technickú zručnosť. Potreba udržiavať a zlepšovať chirurgické zručnosti vyžaduje neustály tréning. Súčasné vzdelávacie metódy sa čoraz viac spoliehajú na simulačné technológie, aby sa zlepšila kvalita a bezpečnosť tréningu s čo najnižším rizikom pre pacientov. Integrácia technológie 3D tlače a obrazových dát z CT a MR skenov priniesla nové možnosti na tvorbu vysoko realistických simulačných modelov pre minimálne invazívnu chirurgiu. Tieto modely presne replikujú prostredie, s ktorým sa stretávame napr. pri novorodeneckej chirurgii. V tomto článku uvádzame vlastné skúsenosti s vývojom a tvorbou 3D tlačených syntetických modelov určených na tréning torakoskopickej operácie atrézie pažeráka s tracheoezofageálnou fistulou. Cieľom tohto súhrnného článku je poskytnúť aktuálny prehľad literatúry venujúcej sa syntetickým 3D tlačeným modelom určeným pre tréning minimálne invazívnej detskej chirurgie.
Summary Pediatric surgery is a medical specialty focused on the diagnosis, treatment, and postoperative care of children with congenital and acquired anomalies and diseases. The goal of pediatric surgeons is to ensure that children receive the best possible care while minimizing the risks and complications associated with surgical procedures. Contemporary pediatric surgeons face many challenges, including a decline in the number of children with congenital developmental defects, economic pressures, and efforts to increase efficiency, leading to reduced time spent on individual surgeries. This can limit the opportunity for thorough training of young surgeons. These challenges require innovative approaches and continuous improvement in educational and training methods. Minimally invasive surgery has become a significant part of pediatric surgery, offering benefits such as faster recovery, smaller surgical wounds, and lower risk of infection. However, minimally invasive pediatric surgery is technically demanding and requires excellent technical skills. The need to maintain and improve surgical skills demands ongoing training. Current educational methods increasingly rely on simulation technologies to enhance the quality and safety of training without risk to patients. The integration of 3D printing technology and imaging data from CT and MRI scans has opened new possibilities for creating highly realistic simulation models for minimally invasive surgery. These models accurately replicate the environment encountered in procedures like neonatal surgery. In this article, we present our experience with the development and creation of 3D-printed synthetic models designed for training thoracoscopic surgery of esophageal atresia with tracheoesophageal fistula. The aim of this review article is to provide an up-to-date overview of the literature on synthetic 3D-printed models designed for training in minimally invasive pediatric surgery.
Autosomal dominant craniometaphyseal dysplasia (AD-CMD) is a rare condition defined by the occurrence of progressive diffuse hyperostosis of cranial bones and abnormal metaphyseal widening of the tubular bones. ANKH is known to be the only gene associated with AD-CMD. We present a case of a toddler boy with macrodolichocephaly, asymmetry of the skull, wide bulging forehead, gingival hypertrophy and irregular teeth. Physical examination, X-ray and DNA analysis were performed. All exons and flanking intron regions of ANKH were amplified by PCR and directly sequenced using the Sanger method. X-ray images showed diffuse osteosclerosis in the area of facial skeleton and skull base. Limbs exhibited club-shaped enlargement of the distal metaphysis of the femur and the proximal metaphysis of the tibia were described. The DNA analysis showed that the patient is a heterozygous carrier of the known pathogenic in-frame deletion (rs121908406; ANKH:c.1122-4delCTC, p.Ser375del), which has already been described in patients with AD-CMD.
- MeSH
- Hyperostosis MeSH
- Hypertelorism MeSH
- Infant MeSH
- Craniofacial Abnormalities genetics diagnostic imaging MeSH
- Humans MeSH
- Phosphate Transport Proteins * genetics MeSH
- Radiography MeSH
- Bone Diseases, Developmental genetics diagnostic imaging diagnosis MeSH
- Check Tag
- Infant MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
Intracellular trafficking involves an intricate machinery of motor complexes, including the dynein complex, to shuttle cargo for autophagolysosomal degradation. Deficiency in dynein axonemal chains, as well as cytoplasmic light and intermediate chains, have been linked with ciliary dyskinesia and skeletal dysplasia. The cytoplasmic dynein 1 heavy chain protein (DYNC1H1) serves as a core complex for retrograde trafficking in neuronal axons. Dominant pathogenic variants in DYNC1H1 have been previously implicated in peripheral neuromuscular disorders (NMD) and neurodevelopmental disorders (NDD). As heavy-chain dynein is ubiquitously expressed, the apparent selectivity of heavy chain dyneinopathy for motor neuronal phenotypes remains currently unaccounted for. Here, we aimed to evaluate the full DYNC1H1-related clinical, molecular and imaging spectrum, including multisystem features and novel phenotypes presenting throughout life. We identified 47 cases from 43 families with pathogenic heterozygous variants in DYNC1H1 (aged 0-59 years) and collected phenotypic data via a comprehensive standardized survey and clinical follow-up appointments. Most patients presented with divergent and previously unrecognized neurological and multisystem features, leading to significant delays in genetic testing and establishing the correct diagnosis. Neurological phenotypes include novel autonomic features, previously rarely described behavioral disorders, movement disorders and periventricular lesions. Sensory neuropathy was identified in nine patients (median age of onset 10.6 years), of which five were only diagnosed after the second decade of life, and three had a progressive age-dependent sensory neuropathy. Novel multisystem features included primary immunodeficiency, bilateral sensorineural hearing loss, organ anomalies and skeletal manifestations, resembling the phenotypic spectrum of other dyneinopathies. We also identified an age-dependent biphasic disease course with developmental regression in the first decade and, following a period of stability, neurodegenerative progression after the second decade of life. Of note, we observed several cases in whom neurodegeneration appeared to be prompted by intercurrent systemic infections with double-stranded DNA viruses (Herpesviridae) or single-stranded RNA viruses (Ross River fever, SARS-CoV-2). Moreover, the disease course appeared to be exacerbated by viral infections regardless of age and/or severity of neurodevelopmental disorder manifestations, indicating a role of dynein in anti-viral immunity and neuronal health. In summary, our findings expand the clinical, imaging and molecular spectrum of pathogenic DYNC1H1 variants beyond motor neuropathy disorders and suggest a life-long continuum and age-related progression due to deficient intracellular trafficking. This study will facilitate early diagnosis and improve counselling and health surveillance of affected patients.
- MeSH
- Cytoplasmic Dyneins * genetics MeSH
- Child MeSH
- Adult MeSH
- Phenotype MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Neurodevelopmental Disorders genetics MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
