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Neural fingerprinting is a method to identify individuals from a group of people. Here, we established a new connectome-based identification model and used diffusion maps to show that biological parent-child couples share functional connectivity patterns while listening to stories. These shared fingerprints enabled the identification of children and their biological parents from a group of parents and children. Functional patterns were evident in both cognitive and sensory brain networks. Defining "typical" shared biological parent-child brain patterns may enable predicting or even preventing impaired parent-child connections that develop due to genetic or environmental causes. Finally, we argue that the proposed framework opens new opportunities to link similarities in connectivity patterns to behavioral, psychological, and medical phenomena among other populations. To our knowledge, this is the first study to reveal the neural fingerprint that represents distinct biological parent-child couples.
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Conectoma , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo , Conectoma/métodos , Pais , Relações Pais-FilhoRESUMO
Deficits in executive functions (EF) are a common comorbidity among adolescents with epilepsy. EF deficits were previously correlated with altered connectivity of the fronto-parietal and cingulo-opercular neural networks. The current study investigated white matter integrity in adolescents with epilepsy (n = 29) relative to healthy controls (n = 19). Participants completed questionnaires, neuropsychological testing, and brain magnetic resonance imaging (MRI) that included diffusion tensor imaging (DTI) sequences. On BRIEF parent-report questionnaires, adolescents with epilepsy demonstrated lower working memory and planning abilities than healthy controls. Among adolescents with epilepsy, DTI measurements revealed lower fractional anisotropy (FA) within the right superior longitudinal fasciculus, forceps minor, and the superior frontal segment of the corpus callosum, and higher FA in the left uncinate fasciculus, compared to healthy controls. Better working memory ability in the epilepsy group was associated with higher FA in the superior frontal segment of the corpus callosum. Only in healthy controls, working memory and planning were positively associated with FA values in the left UF, forceps minor and the superior frontal segment of the corpus callosum. The current study complements previous functional studies on the same cohort and suggests that EF impairments among adolescents with epilepsy may be related to the altered anatomical organization of white matter tracts. Combining structural and functional data could potentially enrich the neuropsychological assessment of executive functioning in adolescents with epilepsy.
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Epilepsy, a prevalent neurological disorder, profoundly affects patients' quality of life due to the unpredictable nature of seizures. The development of a reliable and user-friendly wearable EEG system capable of detecting and predicting seizures has the potential to revolutionize epilepsy care. However, optimizing electrode configurations for such systems, which is crucial for balancing accuracy and practicality, remains to be explored. This study addresses this gap by developing a systematic approach to optimize electrode configurations for a seizure detection machine-learning algorithm. Our approach was applied to an extensive database of prolonged annotated EEG recordings from 158 epilepsy patients. Multiple electrode configurations ranging from one to eighteen were assessed to determine the optimal number of electrodes. Results indicated that the performance was initially maintained as the number of electrodes decreased, but a drop in performance was found to have occurred at around eight electrodes. Subsequently, a comprehensive analysis of all eight-electrode configurations was conducted using a computationally intensive workflow to identify the optimal configurations. This approach can inform the mechanical design process of an EEG system that balances seizure detection accuracy with the ease of use and portability. Additionally, this framework holds potential for optimizing hardware in other machine learning applications. The study presents a significant step towards the development of an efficient wearable EEG system for seizure detection.
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Epilepsia , Dispositivos Eletrônicos Vestíveis , Humanos , Qualidade de Vida , Eletroencefalografia/métodos , Convulsões/diagnóstico , Epilepsia/diagnóstico , Algoritmos , Aprendizado de Máquina , EletrodosRESUMO
BRAT1 biallelic variants are associated with rigidity and multifocal seizure syndrome, lethal neonatal (RMFSL), and neurodevelopmental disorder associating cerebellar atrophy with or without seizures syndrome (NEDCAS). To date, forty individuals have been reported in the literature. We collected clinical and molecular data from 57 additional cases allowing us to study a large cohort of 97 individuals and draw phenotype-genotype correlations. Fifty-nine individuals presented with BRAT1-related RMFSL phenotype. Most of them had no psychomotor acquisition (100%), epilepsy (100%), microcephaly (91%), limb rigidity (93%), and died prematurely (93%). Thirty-eight individuals presented a non-lethal phenotype of BRAT1-related NEDCAS phenotype. Seventy-six percent of the patients in this group were able to walk and 68% were able to say at least a few words. Most of them had cerebellar ataxia (82%), axial hypotonia (79%) and cerebellar atrophy (100%). Genotype-phenotype correlations in our cohort revealed that biallelic nonsense, frameshift or inframe deletion/insertion variants result in the severe BRAT1-related RMFSL phenotype (46/46; 100%). In contrast, genotypes with at least one missense were more likely associated with NEDCAS (28/34; 82%). The phenotype of patients carrying splice variants was variable: 41% presented with RMFSL (7/17) and 59% with NEDCAS (10/17).
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Epilepsia , Doenças Neurodegenerativas , Humanos , Proteínas Nucleares/genética , Epilepsia/genética , Fenótipo , Genótipo , Estudos de Associação Genética , Doenças Neurodegenerativas/genética , AtrofiaRESUMO
Niemann-Pick disease type C (NPC) is a rare autosomal recessive neuro-visceral lipid storage disease. We describe nine cases of infantile-onset NPC with various genetic mutations in the NPC1 gene, which presented with neonatal cholestasis. Serum alpha-fetoprotein (AFP) levels were obtained as part of their workup during the first four months of life. In eight of nine (89%) patients, serum AFP demonstrated elevated levels. Seven infants displayed marked elevations, ranging from 4 to 300 times the upper limit for age-adjusted norms. In most patients, AFP levels peaked during the initial test and declined over time as cholestasis resolved. We conclude that elevated AFP levels are a common, although non-specific, marker for NPC-associated liver disease. These findings demonstrate the benefit of including AFP levels in the workup of neonatal liver disease, especially if there is accompanied cholestasis and if NPC is suspected.
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OBJECTIVE: The aim of the study was to describe focal epilepsy in patients with Laron syndrome (LS). METHODS: Data were retrieved from medical records of a single-center cohort of 75 patients with LS. RESULTS: We describe for the first time 4 patients with concomitant focal epilepsy and LS. Two of them experienced episodes of status epilepticus. Electroencephalogram examination in all 4 patients showed interictal epileptiform discharges in the temporal regions. Three achieved long-term seizure freedom on antiseizure medications. CONCLUSION: Patients with LS may be at risk of developing focal epilepsy, which seems to be unrelated to hypoglycemic episodes in childhood.
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Epilepsias Parciais , Síndrome de Laron , Eletroencefalografia , Epilepsias Parciais/complicações , Epilepsias Parciais/diagnóstico , Epilepsias Parciais/tratamento farmacológico , Humanos , Estudos Retrospectivos , Convulsões/complicações , Convulsões/diagnósticoRESUMO
AIM: This specific review aims to expose clinicians, researchers and administrators in hospitals to the importance, procedures and safety of fMRI studies to promote the increased utilisation of such studies in different geographical places worldwide. The child's brain is developing rapidly, both structurally and functionally. These functional changes can only be detected using functional scans generated from an MRI machine and referred to as a functional MRI (fMRI). This method may be used clinically in complex medical and surgical conditions (e.g., epilepsy surgery), but these days are often used for research purposes. However, due to ethical and logistical considerations, fMRI in the paediatric population is not widely and equally used in different geographical places. CONCLUSIONS: The benefits of using this method to define the functional changes occurring in the developing brain are discussed in this review, along with desensitisation methods recommended when working with this vulnerable population in research and even in a clinical setting.
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Epilepsia , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Criança , Epilepsia/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/efeitos adversos , Pesquisadores , Populações VulneráveisRESUMO
BACKGROUND: Sedation may be necessary for performing electroencephalograms in children with autistic spectrum disorder, however, our sedation success rate using triclofos sodium (TFS) is limited. Intra-nasal dexmedetomidine (IN-DEX) may be a superior sedative for these children. OBJECTIVE: Compare IN-DEX with TFS for sedation efficacy, resistance to drug delivery and adverse events in children with autism undergoing an electroencephalogram. STUDY DESIGN: A single center, prospective observational study of children with autism sedated for electroencephalograms using IN-DEX compared to an age matched, historic group of children with autism, sedated for electroencephalograms using TFS. RESULTS: Characteristics of 41 IN-DEX sedations were compared to 41 TFS sedations in 82 ASD children. Epileptiform discharges were demonstrated in 23/82 (28%) of children in the cohort. Sedation depth by UMSS was significantly deeper in the IN-DEX group (2.49 ± 0.78 vs. 1.41 ± 0.89, p < 0.001). Electroencephalogram quality demonstrated less motion artifact in the IN-DEX group (1.75 ± 0.76 vs. 2.18 ± 0.88, p < 0.001). The rate of very poor or sedation failure was significantly lower in the IN-DEX group (17% vs 56.1%, p < 0.001), RR = 0.3 (95% CI 0.15 to 0.63, p < 0.001). No major adverse events were documented in either group. Bradycardia occurred in 8/41(19.5%) of children in IN-DEX group and none in TFS group (p = 0.003). Hypotension or poor perfusion were not demonstrated in either group. CONCLUSION: In children with autism undergoing electroencephalograms, IN-DEX was more tolerable than TFS, induced deeper sedation with a greater success rate, and improved electroencephalogram quality. Both sedatives were equally safe in this population.
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Transtorno Autístico , Dexmedetomidina , Transtorno Autístico/tratamento farmacológico , Criança , Dexmedetomidina/efeitos adversos , Eletroencefalografia , Humanos , Hipnóticos e Sedativos , Organofosfatos , SódioRESUMO
PURPOSE: When performed correctly, hyperventilation (HV) for three minutes provokes absence seizures in virtually all children, a finding suggestive of a diagnosis of childhood absence epilepsy (CAE). Interestingly, some children experience absence seizures while performing HV in the office yet do not experience absences during HV on subsequent routine EEG. In most instances, HV during routine EEG is performed in the supine position, while in the office HV is done with the child sitting-up. Therefore, we hypothesized that the position in which HV is performed may influence its yield in provoking absence seizures. METHODS: We conducted a randomized multi-center controlled trial among children (4-10 years old) with suspected CAE. During a routine EEG, children were asked to perform HV twice, in the supine and sitting positions. RESULTS: Twenty children (four males) diagnosed with CAE were included in the analysis. Seventeen of the 20 patients experienced absence seizures while sitting and 13 experienced seizures during supine HV (p = 0.031). All patients that had absence seizures during supine HV also had seizures during sitting HV. Among patients with absences in both positions, seizure duration was significantly shorter during sitting HV (mean 8.69 seconds) than during supine HV (mean 12 seconds) (p = 0.042). An opposite tendency was seen in the younger age group (4-7 years), with shorter seizures in the supine HV group (5.6 seconds supine, 7.57 seconds sitting, p = 0.019). CONCLUSIONS: HV in the sitting position may increase the yield of provoking absence seizures during routine EEGs, thereby improving its sensitivity in the diagnosis of CAE.
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Eletroencefalografia/métodos , Epilepsia Tipo Ausência/diagnóstico , Hiperventilação , Convulsões , Postura Sentada , Decúbito Dorsal , Criança , Pré-Escolar , Eletroencefalografia/normas , Feminino , Humanos , Hiperventilação/complicações , Masculino , Convulsões/etiologia , Sensibilidade e Especificidade , Fatores de TempoRESUMO
AIM: This study aimed to define whether individuals with drug-resistant focal epilepsy also used regions related to cognitive control to facilitate reading. METHODS: We focused on patients with drug-resistant focal epilepsy in 2011-2014, who were aged 8-20 years and were being treated at the Cincinnati Children's Hospital, USA. They performed a verb generation functional magnetic resonance imaging task known to involve language and cognitive control, as well as a formal reading assessment. The reading scores were correlated with functional connectivity of the anterior cingulate cortex (ACC) using seed-to-voxel analysis. RESULTS: There were 81 potential patients and 13 (seven females) met the inclusion criteria. Their age at seizure onset was 0-13 years, and they had a mean age of 12.66 ± 3.17 years at the time of the study. Individuals with epilepsy demonstrated average intelligence and word reading ability. Their reading scores were positively correlated with functional connectivity between the ACC and regions related to emotional processing (right amygdala), learning and language processing (left cerebellum) and visual processing. CONCLUSION: Our results support the role that the ACC plays in proficient reading among children with drug-resistant epilepsy, even in those with epileptogenic foci in areas related to language.
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Preparações Farmacêuticas , Leitura , Adolescente , Adulto , Encéfalo , Mapeamento Encefálico , Criança , Cognição , Feminino , Humanos , Imageamento por Ressonância Magnética , Adulto JovemRESUMO
AIM: Triclofos sodium (TFS) has been used for many years in children as a sedative for painless medical procedures. It is physiologically and pharmacologically similar to chloral hydrate, which has been censured for use in children with neurocognitive disorders. The aim of this study was to investigate the safety and efficacy of TFS sedation in a pediatric population with a high rate of neurocognitive disability. METHODS: The database of the neurodiagnostic institute of a tertiary academic pediatric medical center was retrospectively reviewed for all children who underwent sedation with TFS in 2014. Data were collected on demographics, comorbidities, neurologic symptoms, sedation-related variables, and outcome. RESULTS: The study population consisted of 869 children (58.2% male) of median age 25 months (range 5-200 months); 364 (41.2%) had neurocognitive diagnoses, mainly seizures/epilepsy, hypotonia, or developmental delay. TFS was used for routine electroencephalography in 486 (53.8%) patients and audiometry in 401 (46.2%). Mean (± SD) dose of TFS was 50.2 ± 4.9 mg/kg. Median time to sedation was 45 min (range 5-245), and median duration of sedation was 35 min (range 5-190). Adequate sedation depth was achieved in 769 cases (88.5%). Rates of sedation-related adverse events were low: apnea, 0; desaturation ≤ 90%, 0.2% (two patients); and emesis, 0.35% (three patients). None of the children had hemodynamic instability or signs of poor perfusion. There was no association between desaturations and the presence of hypotonia or developmental delay. CONCLUSION: TFS, when administered in a controlled and monitored environment, may be safe for use in children, including those with underlying neurocognitive disorders.
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Hipnóticos e Sedativos/uso terapêutico , Doenças do Sistema Nervoso/tratamento farmacológico , Organofosfatos/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Hipnóticos e Sedativos/farmacologia , Lactente , Masculino , Organofosfatos/farmacologiaRESUMO
BACKGROUND: Early-onset epileptic encephalopathy (EOEE) is a severe convulsive disorder with a poor developmental prognosis. Although it has been associated with mutations in a number of genes, the fact that there is a large proportion of patients who remain undiagnosed suggests that there are many more still-unknown genetic causes of EOEE. Achieving a genetic diagnosis is important for understanding the biological basis of the disease, with its implications for treatment and family planning. METHODS: Whole-exome sequencing was performed in a family of Ashkenazi Jewish origin in which a male infant was diagnosed with EOEE. There was no family history of a similar neurologic disease. The patient had extreme hypotonia, neonatal hypothermia, choreiform movements, and vision impairment in addition to the convulsive disorder. RESULTS: A de novo heterozygous missense mutation, c.1003A > C, p.Asn335His, was identified in a conserved domain of GABRA2. GABRA2 encodes the α2 subunit of the GABAA receptor. CONCLUSIONS: In the context of previous reports of an association of de novo mutations in genes encoding different subunits of the GABAA receptor (GABRB1, GABRA1, GABRG2, GABRB3) with autosomal dominant epileptic disorders, we conclude that a de novo mutation in GABRA2 is likely to cause autosomal dominant EOEE accompanied by a movement disorder and vision impairment.
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Coreia/genética , Epilepsia Generalizada/genética , Receptores de GABA-A/genética , Humanos , Lactente , Masculino , Mutação de Sentido IncorretoRESUMO
We examined gut transit in 7 young adults (18-24 years of age) with Duchenne muscular dystrophy using wireless motility capsules. Total and segmental gut transit times were normal in essentially all patients. Our study using a validated tool suggests normal transit constipation as the pathophysiologic basis for constipation in Duchenne muscular dystrophy.
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Endoscopia por Cápsula/métodos , Constipação Intestinal/fisiopatologia , Trânsito Gastrointestinal/fisiologia , Distrofia Muscular de Duchenne/fisiopatologia , Adolescente , Adulto , Humanos , Masculino , Adulto JovemRESUMO
Cutis laxa syndromes are rare inherited disorders of skin and connective tissue metabolism associated with variable systemic involvement. The main clinical manifestation is loose, wrinkled, redundant, inelastic skin, hypotonia, typical facies including short nose and down-slanting palpebral fissures, and varying degrees of developmental delay. The aim of this report is to describe two siblings diagnosed with a moderate form of ATP6V0A2-related cutis laxa with polymicrogyria (cobblestone-like brain dysgenesis). One of the patients has myoclonic epilepsy which may have contributed to his more severe clinical presentation. The literature on cutis laxa syndromes is reviewed.
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Cútis Laxa/patologia , Cútis Laxa/fisiopatologia , Epilepsias Mioclônicas/patologia , Epilepsias Mioclônicas/fisiopatologia , Polimicrogiria/patologia , Polimicrogiria/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , Criança , Cútis Laxa/complicações , Cútis Laxa/diagnóstico por imagem , Epilepsias Mioclônicas/complicações , Epilepsias Mioclônicas/diagnóstico por imagem , Feminino , Humanos , Masculino , Mutação , Polimicrogiria/complicações , Polimicrogiria/diagnóstico por imagem , IrmãosRESUMO
OBJECTIVES: To determine the prevalence and clinical characteristics of constipation among patients with Duchenne muscular dystrophy (DMD). STUDY DESIGN: This cross-sectional prospective study included 120 patients (age range 5-30 years old) with an established diagnosis of DMD. Participants filled out the constipation section of a validated Questionnaire on Pediatric Gastrointestinal Symptoms based on Rome-III Criteria (QPGS-RIII) for the diagnosis of functional constipation as part of a routine clinic visit. We evaluated several potential screening methods for constipation: the Bristol stool form scale, routine physical examination, and fecal load on abdominal radiograph. These methods were compared with the QPGS-RIII in diagnosing functional constipation. Risk factors for the development of functional constipation were determined. RESULTS: Based on the QPGS-RIII, 46.7% of patients with DMD in this cohort were diagnosed with functional constipation. Prevalence was not affected by age or functional status. None of the screening methods tested were sensitive enough to diagnose functional constipation. Among patients with constipation, only 43.6% received specific treatment for constipation and only one-half of these treated patients reported resolution of constipation. CONCLUSIONS: This study systematically examined constipation among patients with DMD and provides evidence that constipation among patients with DMD is highly prevalent, underdiagnosed, and undertreated. QPGS-RIII is easy to administer and is an efficient tool to diagnose functional constipation in patients with DMD in a clinic setting.
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Constipação Intestinal/complicações , Distrofia Muscular de Duchenne/complicações , Adolescente , Adulto , Criança , Pré-Escolar , Constipação Intestinal/epidemiologia , Constipação Intestinal/terapia , Estudos Transversais , Feminino , Humanos , Masculino , Programas de Rastreamento , Distrofia Muscular de Duchenne/epidemiologia , Distrofia Muscular de Duchenne/terapia , Prevalência , Estudos Prospectivos , Fatores de Risco , Sensibilidade e Especificidade , Inquéritos e Questionários , Adulto JovemRESUMO
INTRODUCTION: Individuals with dyslexia exhibit associated learning deficits and impaired executive functions. The Wisconsin Card Sorting Test (WCST) is a learning-based task that relies heavily on executive functioning, in particular, attention shift and working memory. Performance during early and late phases of a series within the task represents learning and implementation of a newly learned rule. Here, we aimed to examine two event-related potentials associated with learning, feedback-related negativity (FRN)-P300 complex, in individuals with dyslexia performing the WCST. METHODS: Adolescents with dyslexia and age-matched typical readers performed the Madrid card sorting test (MCST), a computerized version of the WCST. Task performance, reading measures, and cognitive measures were collected. FRN and the P300 complex were acquired using the event-related potentials methodology and were compared in early vs late errors within a series. RESULTS: While performing the MCST, both groups showed a significant reduction in average reaction times and a trend toward decreased error rates. Typical readers performed consistently better than individuals with dyslexia. FRN amplitudes in early phases were significantly smaller in dyslexic readers, but were essentially equivalent to typical readers in the late phase. P300 amplitudes were initially smaller among readers with dyslexia and tended to decrease further in late phases. Differences in FRN amplitudes for early vs late phases were positively correlated with those of P300 amplitudes in the entire sample. CONCLUSION: Individuals with dyslexia demonstrate a behavioral and electrophysiological change within single series of the MCST. However, learning patterns seem to differ between individuals with dyslexia and typical readers. We attribute these differences to the lower baseline performance of individuals with dyslexia. We suggest that these changes represent a fast compensatory mechanism, demonstrating the importance of learning strategies on reading among individuals with dyslexia.
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Dislexia/fisiopatologia , Eletroencefalografia , Potenciais Evocados P300 , Retroalimentação Psicológica , Aprendizagem/fisiologia , Adolescente , Dislexia/psicologia , Feminino , Humanos , Masculino , Memória de Curto Prazo , Tempo de ReaçãoRESUMO
Schilder's disease (SD) is a rare variant of multiple sclerosis with a predilection to children. It is characterized by focal neurological abnormalities, which are atypical for MS, in conjunction with tumor-like white matter lesions on MRI. We report the case of an 11-year-old girl that demonstrates two important features of the disease: a) the clinical presentation and subsequent course in conjunction with the serial neuroradiological findings stress the feasibility of a non-invasive diagnosis of SD; and b) we report a significant clinical response to treatment with intravenous human Immunoglobulins.