RESUMO
OBJECTIVE: To describe the rare complication of cerebral pseudoaneurysm formation following stereotactic electroencephalography (sEEG) lead implantation in children. METHODS: A retrospective chart review of all pediatric patients undergoing sEEG procedures between 2015 and 2020 was performed. Cases of pseudoaneurysm were identified and reviewed. RESULTS: Cerebral pseudoaneurysms were identified in two of 58 total cases and 610 implanted electrodes. One lesion was detected 1 year after sEEG explantation and required craniotomy and clipping. The other was detected 3 months post-explantation and underwent coil embolization. Neither patient had any neurologic deficits associated with the pseudoaneurysm before or after treatment. CONCLUSIONS: Pseudoaneurysm formation post-sEEG explantation is rare and likely underreported. Routine, post-explantation/treatment imaging is warranted to detect this rare but potentially lethal complication.
Assuntos
Falso Aneurisma , Humanos , Criança , Estudos Retrospectivos , Eletroencefalografia/métodos , Técnicas Estereotáxicas , Imageamento Tridimensional , Eletrodos ImplantadosRESUMO
Malformations of cortical development (MCD) are neurological conditions involving focal disruptions of cortical architecture and cellular organization that arise during embryogenesis, largely from somatic mosaic mutations, and cause intractable epilepsy. Identifying the genetic causes of MCD has been a challenge, as mutations remain at low allelic fractions in brain tissue resected to treat condition-related epilepsy. Here we report a genetic landscape from 283 brain resections, identifying 69 mutated genes through intensive profiling of somatic mutations, combining whole-exome and targeted-amplicon sequencing with functional validation including in utero electroporation of mice and single-nucleus RNA sequencing. Genotype-phenotype correlation analysis elucidated specific MCD gene sets associated with distinct pathophysiological and clinical phenotypes. The unique single-cell level spatiotemporal expression patterns of mutated genes in control and patient brains indicate critical roles in excitatory neurogenic pools during brain development and in promoting neuronal hyperexcitability after birth.
Assuntos
Epilepsia , Malformações do Desenvolvimento Cortical , Humanos , Multiômica , Encéfalo/metabolismo , Epilepsia/genética , Mutação , Malformações do Desenvolvimento Cortical/genética , Malformações do Desenvolvimento Cortical/metabolismoRESUMO
In analyzing the neural correlates of naturalistic and unstructured behaviors, features of neural activity that are ignored in a trial-based experimental paradigm can be more fully studied and investigated. Here, we analyze neural activity from two patients using electrocorticography (ECoG) and stereo-electroencephalography (sEEG) recordings, and reveal that multiple neural signal characteristics exist that discriminate between unstructured and naturalistic behavioral states such as "engaging in dialogue" and "using electronics". Using the high gamma amplitude as an estimate of neuronal firing rate, we demonstrate that behavioral states in a naturalistic setting are discriminable based on long-term mean shifts, variance shifts, and differences in the specific neural activity's covariance structure. Both the rapid and slow changes in high gamma band activity separate unstructured behavioral states. We also use Gaussian process factor analysis (GPFA) to show the existence of salient spatiotemporal features with variable smoothness in time. Further, we demonstrate that both temporally smooth and stochastic spatiotemporal activity can be used to differentiate unstructured behavioral states. This is the first attempt to elucidate how different neural signal features contain information about behavioral states collected outside the conventional experimental paradigm.
Assuntos
Eletrocorticografia , Eletroencefalografia , Mapeamento Encefálico , Humanos , Distribuição NormalRESUMO
Iron-sulfur cluster proteins are involved in critical functions for gene expression regulation and mitochondrial bioenergetics including the oxidative phosphorylation system. The c.215G>A p.(Arg72Gln) variant in NFS1 has been previously reported to cause infantile mitochondrial complex II and III deficiency. We describe three additional unrelated patients with the same missense variant. Two infants with the same homozygous variant presented with hypotonia, weakness and lactic acidosis, and one patient with compound heterozygous p.(Arg72Gln) and p.(Arg412His) variants presented as a young adult with gastrointestinal symptoms and fatigue. Skeletal muscle biopsy from patients 1 and 3 showed abnormal mitochondrial morphology, and functional analyses demonstrated decreased activity in respiratory chain complex II and variably in complexes I and III. We found decreased mitochondrial and cytosolic aconitase activities but only mildly affected lipoylation of pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase enzymes. Our studies expand the phenotypic spectrum and provide further evidence for the pathogenicity and functional sequelae of NFS1-related disorders with disturbances in both mitochondrial and cytosolic iron-sulfur cluster containing enzymes.
Assuntos
Proteínas Ferro-Enxofre , Ferro , Liases de Carbono-Enxofre/genética , Liases de Carbono-Enxofre/metabolismo , Complexo I de Transporte de Elétrons/metabolismo , Humanos , Ferro/metabolismo , Proteínas Ferro-Enxofre/genética , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Enxofre/metabolismo , Adulto JovemAssuntos
Antirreumáticos/farmacologia , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Síndromes Epilépticas/tratamento farmacológico , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Estado Epiléptico/tratamento farmacológico , Antirreumáticos/administração & dosagem , Criança , Epilepsia Resistente a Medicamentos/diagnóstico , Eletroencefalografia , Síndromes Epilépticas/diagnóstico , Síndromes Epilépticas/etiologia , Feminino , Febre/complicações , Humanos , Infecções/complicações , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Estado Epiléptico/diagnósticoRESUMO
Telehealth's first literature reference is an article in 1879 in the Lancet about using the telephone to reduce unnecessary office visits (Institute of Medicine & Board on Health Care Services, 2012). However, providers have been slow to adopt telehealth into their clinical practice secondary to barriers such as cost and reimbursement (Kane and Gillis, 2018) [2]. The advent of shelter in place orders combined with the ongoing need defined by the Centers for Medicare & Medicaid Services (CMS) Administrator Seema Verma "for all Americans, and particularly vulnerable populations who are at heightened risk, to be able to access their providers" has resulted in the rapid implementation of telehealth across multiple specialties. The goal of this paper is to provide a practical framework for translating quality care in epilepsy as defined by the American Academy of Neurology (AAN) guidelines into a virtual care environment. We will also discuss the use and limitations of point of care testing in epilepsy management.
Assuntos
Betacoronavirus , Infecções por Coronavirus , Epilepsia/terapia , Pandemias , Pneumonia Viral , Telemedicina , COVID-19 , Criança , Humanos , SARS-CoV-2 , Convulsões/terapia , Fatores de TempoRESUMO
BACKGROUND: Nonlesional cingulate gyrus epilepsy is rare, difficult to diagnose, and challenging to treat. METHODS: We report the use of ROSA (Medtech Surgical, Inc., New York, NY, USA) robotic assistance for stereotactic EEG (S-EEG) localization and therapeutic thermal laser ablation of a nonlesional cingulate gyrus epileptogenic zone in a 17-year-old female with intractable partial epilepsy. RESULTS: After an inconclusive exhaustive initial workup, robotic-assisted S-EEG localized the patient's seizure focus to the right cingulate gyrus. Robotic-assisted lesioning of the cingulate gyrus was performed via 5 total ablations with 3 minimally invasive catheters. There were no perioperative complications. The patient was discharged home on postoperative day 2 at her neurologic baseline. She was seizure free for 8 months postoperatively, with a sustained partial response through the 23-month follow-up. CONCLUSIONS: This report expands the technical uses, pathologies, and patient populations being treated via robotic-assisted neurosurgery.
Assuntos
Epilepsia Resistente a Medicamentos/cirurgia , Eletroencefalografia/métodos , Epilepsias Parciais/cirurgia , Giro do Cíngulo/cirurgia , Terapia a Laser/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Adolescente , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsias Parciais/diagnóstico por imagem , Feminino , Giro do Cíngulo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodosRESUMO
OBJECTIVE: Current brain-computer interface (BCI) studies demonstrate the potential to decode neural signals obtained from structured and trial-based tasks to drive actuators with high performance within the context of these tasks. Ideally, to maximize utility, such systems will be applied to a wide range of behavioral settings or contexts. Thus, we explore the potential to augment such systems with the ability to decode abstract behavioral contextual states from neural activity. APPROACH: To demonstrate the feasibility of such context decoding, we used electrocorticography (ECoG) and stereo-electroencephalography (sEEG) data recorded from the cortical surface and deeper brain structures, respectively, continuously across multiple days from three subjects. During this time, the subjects were engaged in a range of naturalistic behaviors in a hospital environment. Behavioral contexts were labeled manually from video and audio recordings; four states were considered: engaging in dialogue, rest, using electronics, and watching television. We decode these behaviors using a factor analysis and support vector machine (SVM) approach. MAIN RESULTS: We demonstrate that these general behaviors can be decoded with high accuracies of 73% for a four-class classifier for one subject and 71% and 62% for a three-class classifier for two subjects. SIGNIFICANCE: To our knowledge, this is the first demonstration of the potential to disambiguate abstract naturalistic behavioral contexts from neural activity recorded throughout the day from implanted electrodes. This work motivates further study of context decoding for BCI applications using continuously recorded naturalistic activity in the clinical setting.
Assuntos
Comportamento/fisiologia , Interfaces Cérebro-Computador , Córtex Cerebral/fisiologia , Eletrocorticografia/métodos , Eletroencefalografia/métodos , Desempenho Psicomotor/fisiologia , Adolescente , Adulto , Eletrodos Implantados , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Reliable posture labels in hospital environments can augment research studies on neural correlates to natural behaviors and clinical applications that monitor patient activity. However, many existing pose estimation frameworks are not calibrated for these unpredictable settings. In this paper, we propose a semi-automated approach for improving upper-body pose estimation in noisy clinical environments, whereby we adapt and build around an existing joint tracking framework to improve its robustness to environmental uncertainties. The proposed framework uses subject-specific convolutional neural network models trained on a subset of a patient's RGB video recording chosen to maximize the feature variance of each joint. Furthermore, by compensating for scene lighting changes and by refining the predicted joint trajectories through a Kalman filter with fitted noise parameters, the extended system yields more consistent and accurate posture annotations when compared with the two state-of-the-art generalized pose tracking algorithms for three hospital patients recorded in two research clinics.
RESUMO
OBJECTIVE: To evaluate factors during acute presumed childhood encephalitis that are associated with development of long-term neurological sequelae. METHODS: A total of 217 patients from Rady Children's Hospital San Diego with suspected encephalitis who met criteria for the California Encephalitis Project were identified. A cohort of 99 patients (40 females, 59 males, age 2 months-17 years) without preexisting neurological conditions, including prior seizures or abnormal brain magnetic resonance imaging scans was studied. Mean duration of follow-up was 29 months. Factors that had a relationship with the development of neurological sequelae (defined as developmental delay, learning difficulties, behavioral problems, or focal neurological findings) after acute encephalitis were identified. RESULTS: Neurological sequelae at follow-up was associated with younger age (6.56 versus 9.22 years) at presentation (P = 0.04) as well as an initial presenting sign of seizure (P = 0.03). Duration of hospital stay (median of 7 versus 15.5 days; P = 0.02) was associated with neurological sequelae. Of the patients with neurological sequelae, a longer hospital stay was associated with patients of an older age (P = 0.04). Abnormalities on neuroimaging (P = 1.00) or spinal fluid analysis (P = 1.00) were not uniquely associated with neurological sequelae. Children who were readmitted after their acute illness (P = 0.04) were more likely to develop neurological sequelae. There was a strong relationship between the patients who later developed epilepsy and those who developed neurological sequelae (P = 0.02). SIGNIFICANCE: Limited data are available on the long-term neurological outcomes of childhood encephalitis. Almost half of our patients were found to have neurological sequelae at follow-up, indicating the importance of earlier therapies to improve neurological outcome.
Assuntos
Encefalite/epidemiologia , Encefalite/fisiopatologia , Adolescente , Anticonvulsivantes/uso terapêutico , Encéfalo/patologia , Criança , Pré-Escolar , Encefalite/patologia , Encefalite/terapia , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Epilepsia/patologia , Epilepsia/fisiopatologia , Feminino , Seguimentos , Humanos , Lactente , Tempo de Internação , MasculinoRESUMO
OBJECTIVE: To evaluate factors associated with the development of epilepsy after resolution of presumed childhood encephalitis. METHODS: A total of 217 patients with suspected encephalitis who met criteria for the California Encephalitis Project were identified. Evaluable outcome information was available for 99 patients (40 girls, 59 boys, ages 2 months to 17 years) without preexisting neurological conditions, including prior seizures or abnormal brain magnetic resonance imaging scans. We identified factors correlated with the development of epilepsy after resolution of the acute illness. RESULTS: Development of epilepsy was correlated with the initial presenting sign of seizure (P < 0.001). With each additional antiepileptic drug used to control seizures, the odds ratio of developing epilepsy was increased twofold (P < 0.001). An abnormal electroencephalograph (P < 0.05) and longer hospital duration (median of 8 versus 21 days) also correlated with development of epilepsy (P < 0.01). The need for medically induced coma was associated with epilepsy (P < 0.001). Seizures in those patients were particularly refractory, often requiring longer than 24 hours to obtain seizure control. Individuals who required antiepileptic drugs at discharge (P < 0.001) or were readmitted after their acute illness (P < 0.001) were more likely to develop epilepsy. Of our patients who were able to wean antiepileptic drugs after being started during hospitalization, 42% were successfully tapered off within 6 months. CONCLUSIONS: Limited data are available on the risk of developing epilepsy after childhood encephalitis. This is the first study that not only identifies risk factors for the development of epilepsy, but also provides data regarding the success rate of discontinuing antiepileptic medication after resolution of encephalitis.
Assuntos
Encefalite/complicações , Epilepsia/etiologia , Adolescente , Anticonvulsivantes/uso terapêutico , Encéfalo/patologia , Encéfalo/fisiopatologia , Criança , Pré-Escolar , Estudos de Coortes , Eletroencefalografia , Encefalite/epidemiologia , Encefalite/fisiopatologia , Encefalite/terapia , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Epilepsia/fisiopatologia , Feminino , Humanos , Lactente , Tempo de Internação , Imageamento por Ressonância Magnética , Masculino , Fatores de Risco , Convulsões/complicações , Convulsões/tratamento farmacológico , Convulsões/epidemiologia , Convulsões/fisiopatologiaRESUMO
We identified a two-branch consanguineous family in which four affected members (three females and one male) presented with constitutive growth delay, severe psychomotor retardation, microcephaly, cerebellar hypoplasia, and second-degree heart block. They also shared distinct facial features and similar appearance of their hands and feet. Childhood-onset insulin-dependent diabetes mellitus developed in one affected child around the age of 9 years. Molecular analysis excluded mutations in potentially related genes such as PTF1A, EIF2AK3, EOMES, and WDR62. This condition appears to be unique of other known conditions, suggesting a unique clinical entity of autosomal recessive mode of inheritance.
Assuntos
Cerebelo/anormalidades , Genes Recessivos , Cardiopatias Congênitas/genética , Microcefalia/genética , Adolescente , Encéfalo/patologia , Criança , Pré-Escolar , Consanguinidade , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/genética , Fácies , Feminino , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Microcefalia/complicações , Microcefalia/diagnóstico , Linhagem , Fenótipo , SíndromeRESUMO
Disorders within the "ciliopathy" spectrum include Joubert (JS), Bardet-Biedl syndromes (BBS), and nephronophthisis (NPHP). Although mutations in single ciliopathy genes can lead to these different syndromes between families, there have been no reports of phenotypic discordance within a single family. We report on two consanguineous families with discordant ciliopathies in sibling. In Ciliopathy-672, the older child displayed dialysis-dependent NPHP whereas the younger displayed the pathognomonic molar tooth MRI sign (MTS) of JS. A second branch displayed two additional children with NPHP. In Ciliopathy-1491, the oldest child displayed classical features of BBS whereas the two younger children displayed the MTS. Importantly, the children with BBS and NPHP lacked MTS, whereas children with JS lacked obesity or NPHP, and the child with BBS lacked MTS and NPHP. Features common to all three disorders included intellectual disability, postaxial polydactyly, and visual reduction. The variable phenotypic expressivity in this family suggests that genetic modifiers may determine specific clinical features within the ciliopathy spectrum.
Assuntos
Síndrome de Bardet-Biedl/complicações , Síndrome de Bardet-Biedl/genética , Doenças Cerebelares/complicações , Doenças Cerebelares/genética , Doenças Renais Císticas/congênito , Nefropatias/complicações , Nefropatias/genética , Hipotonia Muscular/complicações , Hipotonia Muscular/genética , Transtornos da Motilidade Ocular/complicações , Transtornos da Motilidade Ocular/genética , Adolescente , Síndrome de Bardet-Biedl/diagnóstico , Encéfalo/patologia , Doenças Cerebelares/diagnóstico , Criança , Pré-Escolar , Consanguinidade , Fácies , Feminino , Humanos , Nefropatias/diagnóstico , Doenças Renais Císticas/complicações , Doenças Renais Císticas/diagnóstico , Doenças Renais Císticas/genética , Imageamento por Ressonância Magnética , Masculino , Hipotonia Muscular/diagnóstico , Transtornos da Motilidade Ocular/diagnóstico , Linhagem , FenótipoRESUMO
A group of disorders with disparate symptomatology, including congenital cerebellar ataxia, retinal blindness, liver fibrosis, polycystic kidney disease, and polydactyly, have recently been united under a single disease mechanism called 'ciliopathies'. The ciliopathies are due to defects of the cellular antenna known as the primary cilium, a microtubule-based extension of cellular membranes found in nearly all cell types. Key among these ciliopathies is Joubert syndrome, displaying ataxia, oculomotor apraxia, and mental retardation* with a pathognomonic 'molar tooth sign' on brain magnetic resonance imaging. The importance of ciliary function in neuronal development has been appreciated only in the last decade with the classification of Joubert syndrome as a ciliopathy. This, together with the identification of many of the clinical features of ciliopathies in individuals with Joubert syndrome and the localization of Joubert syndrome's causative gene products at or near the primary cilium, have defined a new class of neurological disease. Cilia are involved in diverse cellular processes including protein trafficking, photoreception, embryonic axis patterning, and cell cycle regulation. Ciliary dysfunction can affect a single tissue or manifest as multi-organ involvement. Ciliary defects have been described in retinopathies such as retinitis pigmentosa and Leber congenital amaurosis (defects in photoreceptor ciliary protein complexes), renal syndromes with nephronophthisis and cystic dysplastic kidneys, and liver conditions such as fibrosis and biliary cirrhosis. Recognizing the diverse presentations of the ciliopathies and screening strategies following diagnosis is an important part of the treatment plan of children with cilia-related disorders.
Assuntos
Doenças Cerebelares/complicações , Doenças Cerebelares/patologia , Cílios/patologia , Apraxias/congênito , Síndrome de Bardet-Biedl , Doenças Cerebelares/classificação , Transtornos da Motilidade Ciliar , Síndrome de Cogan , Anormalidades do Olho , Humanos , Amaurose Congênita de Leber , Imageamento por Ressonância Magnética , Síndromes OrofaciodigitaisRESUMO
Hereditary spastic paraplegia (HSP) represents a large group of neurological disorders characterized by progressive spasticity of the lower limbs. One subtype of HSP shows an autosomal recessive form of inheritance with thin corpus callosum (ARHSP-TCC), and displays genetic heterogeneity with four known loci. We identified a consanguineous Egyptian family with five affected individuals with ARHSP-TCC. We found linkage to the SPG11 locus and identified a novel homozygous p.Q498X stop codon mutation in exon 7 in the SPG11 gene encoding Spatacsin. Cognitive impairment and polyneuropathy, reported as frequent in SPG11, were not evident. This family supports the importance of SPG11 as a frequent cause for ARHSP-TCC, and expands the clinical SPG11 spectrum.