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1.
Fluids Barriers CNS ; 17(1): 55, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32912226

RESUMO

Human coronaviruses are highly pathogenic viruses that pose a serious threat to human health. Examples include the severe acute respiratory syndrome outbreak of 2003 (SARS-CoV-1), the Middle East Respiratory Syndrome (MERS-CoV) outbreak of 2012, and the current SARS-CoV-2 (COVID-19) pandemic. Herein, we review the neurological manifestations of coronaviruses and discuss the potential pathogenic role of blood-brain barrier dysfunction. We present the hypothesis that pre-existing vascular damage (due to aging, cardiovascular disease, diabetes, hypertension or other conditions) facilitates infiltration of the virus into the central nervous system (CNS), increasing neuro-inflammation and the likelihood of neurological symptoms. We also discuss the role of a neuroinflammatory cytokine profile in both blood-brain barrier dysfunction and macrovascular disease (e.g. ischemic stroke and thromboembolism). Future studies are needed to better understand the involvement of the microvasculature in coronavirus neuropathology, and to test the diagnostic potential of minimally-invasive screening tools (e.g. serum biomarkers, fluorescein retinal angiography and dynamic-contrast MRI).


Assuntos
Barreira Hematoencefálica/fisiopatologia , Infecções por Coronavirus/fisiopatologia , Inflamação/fisiopatologia , Microvasos/fisiopatologia , Doenças do Sistema Nervoso/fisiopatologia , Pneumonia Viral/fisiopatologia , Betacoronavirus , Barreira Hematoencefálica/imunologia , Barreira Hematoencefálica/virologia , Doenças Cardiovasculares/fisiopatologia , Infecções por Coronavirus/imunologia , Citocinas/imunologia , Diabetes Mellitus/fisiopatologia , Encefalite/imunologia , Encefalite/fisiopatologia , Humanos , Inflamação/imunologia , Microvasos/imunologia , Doenças do Sistema Nervoso/imunologia , Pandemias , Pneumonia Viral/imunologia , Convulsões/imunologia , Convulsões/fisiopatologia , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/fisiopatologia , Tromboembolia/imunologia , Tromboembolia/fisiopatologia
3.
Am J Hum Genet ; 107(3): 544-554, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32730804

RESUMO

RNA polymerase II interacts with various other complexes and factors to ensure correct initiation, elongation, and termination of mRNA transcription. One of these proteins is SR-related CTD-associated factor 4 (SCAF4), which is important for correct usage of polyA sites for mRNA termination. Using exome sequencing and international matchmaking, we identified nine likely pathogenic germline variants in SCAF4 including two splice-site and seven truncating variants, all residing in the N-terminal two thirds of the protein. Eight of these variants occurred de novo, and one was inherited. Affected individuals demonstrated a variable neurodevelopmental disorder characterized by mild intellectual disability, seizures, behavioral abnormalities, and various skeletal and structural anomalies. Paired-end RNA sequencing on blood lymphocytes of SCAF4-deficient individuals revealed a broad deregulation of more than 9,000 genes and significant differential splicing of more than 2,900 genes, indicating an important role of SCAF4 in mRNA processing. Knockdown of the SCAF4 ortholog CG4266 in the model organism Drosophila melanogaster resulted in impaired locomotor function, learning, and short-term memory. Furthermore, we observed an increased number of active zones in larval neuromuscular junctions, representing large glutamatergic synapses. These observations indicate a role of CG4266 in nervous system development and function and support the implication of SCAF4 in neurodevelopmental phenotypes. In summary, our data show that heterozygous, likely gene-disrupting variants in SCAF4 are causative for a variable neurodevelopmental disorder associated with impaired mRNA processing.


Assuntos
Deficiência Intelectual/genética , Transtornos do Neurodesenvolvimento/genética , Convulsões/genética , Fatores de Processamento de Serina-Arginina/genética , Animais , Criança , Drosophila melanogaster/genética , Feminino , Técnicas de Silenciamento de Genes , Variação Genética/genética , Heterozigoto , Humanos , Deficiência Intelectual/fisiopatologia , Locomoção/genética , Masculino , Mutação/genética , Transtornos do Neurodesenvolvimento/fisiopatologia , RNA Polimerase II/genética , Processamento Pós-Transcricional do RNA/genética , RNA Mensageiro/genética , Convulsões/fisiopatologia , Sequenciamento Completo do Exoma
4.
Neurology ; 95(6): e643-e652, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32690794

RESUMO

OBJECTIVE: To investigate the hypothesis that patients diagnosed with psychogenic nonepileptic seizures (PNES) on video-EEG monitoring (VEM) have increased mortality by comparison to the general population. METHODS: This retrospective cohort study included patients evaluated in VEM units of 3 tertiary hospitals in Melbourne, Australia, between January 1, 1995, and December 31, 2015. Diagnosis was based on consensus opinion of experienced epileptologists and neuropsychiatrists at each hospital. Mortality was determined in patients diagnosed with PNES, epilepsy, or both conditions by linkage to the Australian National Death Index. Lifetime history of psychiatric disorders in PNES was determined from formal neuropsychiatric reports. RESULTS: A total of 5,508 patients underwent VEM. A total of 674 (12.2%) were diagnosed with PNES, 3064 (55.6%) with epilepsy, 175 (3.2%) with both conditions, and 1,595 (29.0%) received other diagnoses or had no diagnosis made. The standardized mortality ratio (SMR) of patients diagnosed with PNES was 2.5 (95% confidence interval [CI] 2.0-3.3). Those younger than 30 had an 8-fold higher risk of death (95% CI 3.4-19.8). Direct comparison revealed no significant difference in mortality rate between diagnostic groups. Among deaths in patients diagnosed with PNES (n = 55), external causes contributed 18%, with 20% of deaths in those younger than 50 years attributed to suicide, and "epilepsy" was recorded as the cause of death in 24%. CONCLUSIONS: Patients diagnosed with PNES have a SMR 2.5 times above the general population, dying at a rate comparable to those with drug-resistant epilepsy. This emphasizes the importance of prompt diagnosis, identification of risk factors, and implementation of appropriate strategies to prevent potential avoidable deaths.


Assuntos
Transtorno Conversivo/mortalidade , Convulsões/mortalidade , Adolescente , Adulto , Distribuição por Idade , Transtornos de Ansiedade/mortalidade , Causas de Morte , Criança , Pré-Escolar , Comorbidade , Transtorno Conversivo/fisiopatologia , Transtorno Depressivo/mortalidade , Grupos Diagnósticos Relacionados , Transtornos Dissociativos/mortalidade , Eletroencefalografia , Epilepsia/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Risco , Convulsões/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/mortalidade , Suicídio/estatística & dados numéricos , Centros de Atenção Terciária/estatística & dados numéricos , Vitória/epidemiologia , Gravação em Vídeo , Adulto Jovem
5.
PLoS One ; 15(7): e0235069, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32628682

RESUMO

BACKGROUND: Pneumonia is the leading cause of death among children and young people (CYP) with severe cerebral palsy (CP). Only a few studies used nomogram for assessing risk factors and the probability of pneumonia. Therefore, we aimed to identify risk factors and devise a nomogram for identifying the probability of severe pneumonia in CYP with severe CP. METHODS: This retrospective nationwide population-based cohort study examined CYP with newly diagnosed severe CP before 18 years old between January 1st, 1997 and December 31st, 2013 and followed them up through December 31st, 2013. The primary endpoint was defined as the occurrence of severe pneumonia with ≥ 5 days of hospitalization. Logistic regression analysis was used for determining demographic factors and comorbidities associated with severe pneumonia. These factors were assigned integer points to create a scoring system to identify children at high risk for severe pneumonia. RESULTS: Among 6,356 CYP with newly diagnosed severe CP, 2,135 (33.59%) had severe pneumonia. Multivariable logistic regression analysis revealed that seven independent predictive factors, namely age <3 years, male sex, and comorbidities of pressure ulcer, gastroesophageal reflux, asthma, seizures, and perinatal complications. A nomogram was devised by employing these seven significant predictive factors. The prediction model presented favorable discrimination performance. CONCLUSIONS: The nomogram revealed that age, male sex, history of pressure ulcer, gastroesophageal reflux, asthma, seizures, and perinatal complications were potential risk factors for severe pneumonia among CYP with severe CP.


Assuntos
Paralisia Cerebral/diagnóstico , Paralisia Cerebral/epidemiologia , Nomogramas , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/epidemiologia , Doença Aguda , Adolescente , Fatores Etários , Asma/diagnóstico , Asma/fisiopatologia , Paralisia Cerebral/complicações , Paralisia Cerebral/mortalidade , Criança , Pré-Escolar , Feminino , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/fisiopatologia , Humanos , Modelos Logísticos , Masculino , Pneumonia Bacteriana/complicações , Pneumonia Bacteriana/mortalidade , Lesão por Pressão/diagnóstico , Lesão por Pressão/fisiopatologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Convulsões/diagnóstico , Convulsões/fisiopatologia , Fatores Sexuais , Análise de Sobrevida , Taiwan/epidemiologia
6.
Hosp Pediatr ; 10(10): 902-905, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32636210

RESUMO

Coronavirus disease (COVID-19) has affected children differently from adults worldwide. Data on the clinical presentation of the infection in children are limited. We present a detailed account of pediatric inpatients infected with severe acute respiratory syndrome coronavirus 2 virus at our institution during widespread local transmission, aiming to understand disease presentation and outcomes. A retrospective chart review was performed of children, ages 0 to 18 years, with a positive polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 on nasopharyngeal specimens admitted to our hospital over a 4-week period. We present clinical data from 22 patients and highlight the variability of the presentation. In our study, most children presented without respiratory illness or symptoms suggestive of COVID-19; many were identified only because of universal testing. Because children may have variable signs and symptoms of COVID-19 infection, targeted testing may miss some cases.


Assuntos
Infecções por Coronavirus/fisiopatologia , Tosse/fisiopatologia , Dispneia/fisiopatologia , Fadiga/fisiopatologia , Febre/fisiopatologia , Pneumonia Viral/fisiopatologia , Convulsões/fisiopatologia , Adolescente , Distribuição por Idade , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Betacoronavirus , Proteína C-Reativa/metabolismo , Criança , Pré-Escolar , Doença Crônica , Técnicas de Laboratório Clínico , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/terapia , Feminino , Cardiopatias/epidemiologia , Hospitalização , Hospitais Pediátricos , Humanos , Lactente , Recém-Nascido , Pneumopatias/epidemiologia , Linfopenia/epidemiologia , Masculino , Programas de Rastreamento , Neoplasias/epidemiologia , Cidade de Nova Iorque/epidemiologia , Ventilação não Invasiva , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/metabolismo , Pneumonia Viral/terapia , Pró-Calcitonina/metabolismo , Respiração Artificial , Estudos Retrospectivos , Distribuição por Sexo , Estados Unidos
7.
Nat Commun ; 11(1): 2785, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503997

RESUMO

While current technology permits inference of dynamic brain networks over long time periods at high temporal resolution, the detailed structure of dynamic network communities during human seizures remains poorly understood. We introduce a new methodology that addresses critical aspects unique to the analysis of dynamic functional networks inferred from noisy data. We propose a dynamic plex percolation method (DPPM) that is robust to edge noise, and yields well-defined spatiotemporal communities that span forward and backwards in time. We show in simulation that DPPM outperforms existing methods in accurately capturing certain stereotypical dynamic community behaviors in noisy situations. We then illustrate the ability of this method to track dynamic community organization during human seizures, using invasive brain voltage recordings at seizure onset. We conjecture that application of this method will yield new targets for surgical treatment of epilepsy, and more generally could provide new insights in other network neuroscience applications.


Assuntos
Encéfalo/fisiopatologia , Rede Nervosa/fisiopatologia , Adulto , Algoritmos , Simulação por Computador , Eletrodos , Humanos , Masculino , Convulsões/fisiopatologia , Fatores de Tempo
9.
Neuron ; 107(3): 417-435, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32579881

RESUMO

Identifying effective treatments for Alzheimer's disease (AD) has proven challenging and has instigated a shift in AD research focus toward the earliest disease-initiating cellular mechanisms. A key insight has been an increase in soluble Aß oligomers in early AD that is causally linked to neuronal and circuit hyperexcitability. However, other accumulating AD-related peptides and proteins, including those derived from the same amyloid precursor protein, such as Aη or sAPPα, and autonomously, such as tau, exhibit surprising opposing effects on circuit dynamics. We propose that the effects of these on neuronal circuits have profound implications for our understanding of disease complexity and heterogeneity and for the development of personalized diagnostic and therapeutic strategies in AD. Here, we highlight important peptide-specific mechanisms of dynamic pathological disequilibrium of cellular and circuit activity in AD and discuss approaches in which these may be further understood, and theoretically and experimentally leveraged, to elucidate AD pathophysiology.


Assuntos
Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Encéfalo/metabolismo , Neurônios/metabolismo , Convulsões/metabolismo , Proteínas tau/metabolismo , Doença de Alzheimer/fisiopatologia , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Astrócitos/metabolismo , Segmento Inicial do Axônio/metabolismo , Encéfalo/fisiopatologia , Humanos , Microglia/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.1/metabolismo , Vias Neurais , Fragmentos de Peptídeos/metabolismo , Receptores de Glutamato/metabolismo , Convulsões/fisiopatologia , Sinapses/metabolismo
10.
Medicine (Baltimore) ; 99(20): e19940, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443294

RESUMO

The aim of this study was to investigate the demographic, clinical, and electrophysiological characteristics of postictal generalized electroencephalography (EEG) suppression (PGES), thereby facilitating the recognition of PGES and providing clues regarding its risk factors, pathophysiology, and relationship with sudden unexpected death in epilepsy patients (SUDEP).We retrospectively reviewed 237 generalized convulsive seizures (GCSs) in 126 patients during long-term video-EEG (VEEG) recordings. The associations of PGES and prolonged PGES (duration >20 seconds) with person- and seizure-specific variables were evaluated independently using SPSS software.Eighty patients (63.5%, 80/126) exhibited PGES after 127 GCSs (53.6%, 127/237) with an average PGES duration of 41.31 ±â€Š24.03 seconds. The tonic phase was significantly prolonged in patients with PGES and prolonged PGES. PGES was independently associated with ictal semiology, which was attributable to the different proportions of GCS type 1. After seizure termination, patients with PGES had a higher percentage of postictal unresponsiveness and immobility, including oropharyngeal immobility. Between prolonged and short-duration PGES, the former was more likely to phase out gradually followed by immediate body movement, whereas the latter tended to have an abrupt, evoked termination followed by delayed body movement.Prolonged tonic duration, GCS type 1, postictal unresponsiveness, and immobility were more prone to occur with PGES, which might imply that hyperactivation of inhibitory neural networks underlies the pathophysiology of PGES and subsequent SUDEP. Any form of periictal bedside care, whether it constitutes effective medical intervention or not, is advisable due to its possible contribution to the interruption of PGES. Regardless of the PGES termination pattern, the neural network resuscitation process was progressive.


Assuntos
Encéfalo/fisiopatologia , Eletroencefalografia , Convulsões/fisiopatologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Estudos Retrospectivos , Adulto Jovem
11.
Pediatrics ; 145(6)2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32385134

RESUMO

BACKGROUND AND OBJECTIVES: There are no US Food and Drug Administration-approved therapies for neonatal seizures. Phenobarbital and phenytoin frequently fail to control seizures. There are concerns about the safety of seizure medications in the developing brain. Levetiracetam has proven efficacy and an excellent safety profile in older patients; therefore, there is great interest in its use in neonates. However, randomized studies have not been performed. Our objectives were to study the efficacy and safety of levetiracetam compared with phenobarbital as a first-line treatment of neonatal seizures. METHODS: The study was a multicenter, randomized, blinded, controlled, phase IIb trial investigating the efficacy and safety of levetiracetam compared with phenobarbital as a first-line treatment for neonatal seizures of any cause. The primary outcome measure was complete seizure freedom for 24 hours, assessed by independent review of the EEGs by 2 neurophysiologists. RESULTS: Eighty percent of patients (24 of 30) randomly assigned to phenobarbital remained seizure free for 24 hours, compared with 28% of patients (15 of 53) randomly assigned to levetiracetam (P < .001; relative risk 0.35 [95% confidence interval: 0.22-0.56]; modified intention-to-treat population). A 7.5% improvement in efficacy was achieved with a dose escalation of levetiracetam from 40 to 60 mg/kg. More adverse effects were seen in subjects randomly assigned to phenobarbital (not statistically significant). CONCLUSIONS: In this phase IIb study, phenobarbital was more effective than levetiracetam for the treatment of neonatal seizures. Higher rates of adverse effects were seen with phenobarbital treatment. Higher-dose studies of levetiracetam are warranted, and definitive studies with long-term outcome measures are needed.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia Neonatal Benigna/tratamento farmacológico , Epilepsia Neonatal Benigna/fisiopatologia , Levetiracetam/uso terapêutico , Fenobarbital/uso terapêutico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Epilepsia Neonatal Benigna/diagnóstico , Feminino , Humanos , Recém-Nascido , Masculino , Convulsões/diagnóstico , Convulsões/tratamento farmacológico , Convulsões/fisiopatologia
12.
Lancet Child Adolesc Health ; 4(6): 435-443, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32450123

RESUMO

BACKGROUND: Individuals with attention-deficit hyperactivity disorder (ADHD) are at increased risk of seizures. Stimulant medications such as methylphenidate are the most commonly prescribed treatment for ADHD, but the association between their therapeutic use and the risk of seizures is unclear. We aimed to investigate the association between methylphenidate treatment and the risk of seizure. METHODS: For this population-based observational study, we used the electronic medical record database of the Hong Kong Clinical Data Analysis And Reporting System to identify individuals aged 6-25 years who received at least one methylphenidate prescription during the study period. Individuals with records of seizure or epilepsy before the study period were excluded. Individuals treated with methylphenidate who had seizures during the study period were included in the subsequent analyses, and a self-controlled case-series design was used to control for time-invariant individual characteristics. We did additional analyses using skin infection as a negative control outcome. We compared relative incidence of seizure during periods when individuals were exposed to methylphenidate with that during non-exposed periods. FINDINGS: Of 29 604 individuals prescribed methylphenidate between Jan 1, 2001, and Dec 31, 2017, 269 (199 males and 70 females) had incident seizures. The mean age at baseline was 6·66 years (SD 2·01) and the median age at the incident seizure was 9·69 years (IQR 7·62-12·99). The overall incidence of seizure during methylphenidate treatment was 4·4 per 10 000 patient-years. We detected an increased risk of seizure during the first 30 days of methylphenidate treatment compared with that during non-exposed periods, with an incidence rate ratio of 4·01 (95% CI 2·09-7·68). No increase in risk was identified during the following 31-180 days of treatment (1·13, 0·56-2·25) or during subsequent treatment (1·38, 0·92-2·07). We did not identify an increased risk in any risk window for the negative control outcome analysis. No individuals died because of a seizure during the study period. INTERPRETATION: The incidence of seizures was higher in the period immediately after the start of methylphenidate treatment than in the non-exposed period. No increased risk was observed during continuation of methylphenidate treatment. The association between methylphenidate treatment and seizures immediately after initiation of medication can be seen as a potential safety signal. Monitoring of neurological outcomes in individuals with ADHD is recommended when they first start methylphenidate treatment. FUNDING: Hong Kong Research Grants Council.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Metilfenidato/efeitos adversos , Convulsões/induzido quimicamente , Convulsões/epidemiologia , Adolescente , Distribuição por Idade , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Criança , Estudos de Coortes , Bases de Dados Factuais , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Hong Kong , Humanos , Incidência , Masculino , Metilfenidato/uso terapêutico , Monitorização Fisiológica , Distribuição de Poisson , Estudos Retrospectivos , Medição de Risco , Convulsões/fisiopatologia , Distribuição por Sexo , Adulto Jovem
13.
Mult Scler Relat Disord ; 43: 102216, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32464585

RESUMO

The new severe acute respiratory syndrome- coronavirus 2 is reported to affect the nervous system. Among the reports of the various neurological manifestations, there are a few documented specific processes to explain the neurological signs. We report a para-infectious encephalitis patient with clinical, laboratory, and imaging findings during evolution and convalescence phase of coronavirus infection. This comprehensive overview can illuminate the natural history of similar cases. As the two previously reported cases of encephalitis associated with this virus were not widely discussed regarding the treatment, we share our successful approach and add some recommendations about this new and scarce entity.


Assuntos
Transtornos da Consciência/fisiopatologia , Infecções por Coronavirus/fisiopatologia , Encefalite/fisiopatologia , Glucocorticoides/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Metilprednisolona/uso terapêutico , Pneumonia Viral/fisiopatologia , Convulsões/fisiopatologia , Adulto , Antibacterianos/uso terapêutico , Anticonvulsivantes/uso terapêutico , Sulfato de Atazanavir/uso terapêutico , Betacoronavirus , Encéfalo/diagnóstico por imagem , Transtornos da Consciência/diagnóstico por imagem , Transtornos da Consciência/etiologia , Transtornos da Consciência/terapia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/terapia , Imagem de Difusão por Ressonância Magnética , Progressão da Doença , Encefalite/diagnóstico por imagem , Encefalite/etiologia , Encefalite/terapia , Feminino , Inibidores da Protease de HIV/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Unidades de Terapia Intensiva , Levetiracetam/uso terapêutico , Pulmão/diagnóstico por imagem , Imagem por Ressonância Magnética , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/terapia , Ponte/diagnóstico por imagem , Respiração Artificial , Convulsões/tratamento farmacológico , Convulsões/etiologia , Lobo Temporal/diagnóstico por imagem , Tálamo/diagnóstico por imagem , Tomografia Computadorizada por Raios X
14.
Neurology ; 94(24): e2567-e2576, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32398358

RESUMO

OBJECTIVE: To test the hypothesis that neurophysiologic biomarkers of muscle activation during convulsive seizures reveal seizure severity and to determine whether automatically computed surface EMG parameters during seizures can predict postictal generalized EEG suppression (PGES), indicating increased risk for sudden unexpected death in epilepsy. Wearable EMG devices have been clinically validated for automated detection of generalized tonic-clonic seizures. Our goal was to use quantitative EMG measurements for seizure characterization and risk assessment. METHODS: Quantitative parameters were computed from surface EMGs recorded during convulsive seizures from deltoid and brachial biceps muscles in patients admitted to long-term video-EEG monitoring. Parameters evaluated were the durations of the seizure phases (tonic, clonic), durations of the clonic bursts and silent periods, and the dynamics of their evolution (slope). We compared them with the duration of the PGES. RESULTS: We found significant correlations between quantitative surface EMG parameters and the duration of PGES (p < 0.001). Stepwise multiple regression analysis identified as independent predictors in deltoid muscle the duration of the clonic phase and in biceps muscle the duration of the tonic-clonic phases, the average silent period, and the slopes of the silent period and clonic bursts. The surface EMG-based algorithm identified seizures at increased risk (PGES ≥20 seconds) with an accuracy of 85%. CONCLUSIONS: Ictal quantitative surface EMG parameters correlate with PGES and may identify seizures at high risk. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that during convulsive seizures, surface EMG parameters are associated with prolonged postictal generalized EEG suppression.


Assuntos
Eletroencefalografia , Eletromiografia , Convulsões/fisiopatologia , Adolescente , Adulto , Algoritmos , Criança , Músculo Deltoide/fisiopatologia , Epilepsia Tônico-Clônica/fisiopatologia , Feminino , Músculos Isquiossurais/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Adulto Jovem
16.
Neurology ; 94(22): e2311-e2322, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32409485

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of adjunctive cenobamate 200 mg/d in patients with uncontrolled focal (partial-onset) seizures despite treatment with 1 to 3 antiepileptic drugs. METHODS: In this multicenter, double-blind, placebo-controlled study, adults 18 to 65 years of age with focal seizures were randomized 1:1 (cenobamate:placebo) after an 8-week baseline period. The 12-week double-blind treatment period consisted of a 6-week titration phase and a 6-week maintenance phase. The primary outcome was percent change in seizure frequency (from baseline) per 28 days during double-blind treatment. RESULTS: Two hundred twenty-two patients were randomized; 113 received cenobamate and 109 received placebo; and 90.3% and 90.8% of patients, respectively, completed double-blind treatment. Median baseline seizure frequency was 6.5 in 28 days (range 0-237). Compared to placebo, cenobamate conferred a greater median percent seizure reduction (55.6% vs 21.5%; p < 0.0001) The responder rate (≥50% reduction in seizure frequency) was 50.4% for cenobamate and 22.2% for placebo (p < 0.0001). Focal seizures with motor component, impaired awareness, and focal to bilateral tonic-clonic seizures were significantly reduced with cenobamate vs placebo. During maintenance, 28.3% of cenobamate-treated and 8.8% of placebo-treated patients were seizure-free. Treatment-emergent adverse events reported in >10% in either group (cenobamate vs placebo) were somnolence (22.1% vs 11.9%), dizziness (22.1% vs 16.5%), headache (12.4% vs 12.8%), nausea (11.5% vs 4.6%), and fatigue (10.6% vs 6.4%). CONCLUSION: Adjunctive treatment with cenobamate 200 mg/d significantly improved seizure control in adults with uncontrolled focal seizures and was well tolerated. CLINICALTRIALSGOV IDENTIFIER: NCT01397968. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that, for patients with uncontrolled focal seizures, adjunctive cenobamate reduces seizures.


Assuntos
Anticonvulsivantes/administração & dosagem , Carbamatos/administração & dosagem , Clorofenóis/administração & dosagem , Convulsões/diagnóstico , Convulsões/tratamento farmacológico , Tetrazóis/administração & dosagem , Adolescente , Adulto , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Convulsões/fisiopatologia , Adulto Jovem
17.
J Med Virol ; 92(7): 699-702, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: covidwho-96729

RESUMO

Neurologic sequelae can be devastating complications of respiratory viral infections. We report the presence of virus in neural and capillary endothelial cells in frontal lobe tissue obtained at postmortem examination from a patient infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Our observations of virus in neural tissue, in conjunction with clinical correlates of worsening neurologic symptoms, pave the way to a closer understanding of the pathogenic mechanisms underlying central nervous system involvement by SARS-CoV-2.


Assuntos
Ageusia/diagnóstico , Ataxia/diagnóstico , Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Transtornos do Olfato/diagnóstico , Pneumonia Viral/diagnóstico , Convulsões/diagnóstico , Idoso , Ageusia/complicações , Ageusia/fisiopatologia , Ageusia/virologia , Ataxia/complicações , Ataxia/fisiopatologia , Ataxia/virologia , Betacoronavirus/genética , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Células Endoteliais/patologia , Células Endoteliais/virologia , Evolução Fatal , Lobo Frontal/irrigação sanguínea , Lobo Frontal/patologia , Lobo Frontal/virologia , Hospitalização , Humanos , Pulmão/irrigação sanguínea , Pulmão/patologia , Pulmão/virologia , Masculino , Neurônios/patologia , Neurônios/virologia , Transtornos do Olfato/complicações , Transtornos do Olfato/fisiopatologia , Transtornos do Olfato/virologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Convulsões/complicações , Convulsões/fisiopatologia , Convulsões/virologia
19.
PLoS One ; 15(4): e0230510, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32240175

RESUMO

The temporal and spectral characteristics of tonic-clonic seizures are investigated using a neural field model of the corticothalamic system in the presence of a temporally varying connection strength between the cerebral cortex and thalamus. Increasing connection strength drives the system into ∼ 10 Hz seizure oscillations once a threshold is passed and a subcritical Hopf bifurcation occurs. In this study, the spectral and temporal characteristics of tonic-clonic seizures are explored as functions of the relevant properties of physiological connection strengths, such as maximum strength, time above threshold, and the ramp rate at which the strength increases or decreases. Analysis shows that the seizure onset time decreases with the maximum connection strength and time above threshold, but increases with the ramp rate. Seizure duration and offset time increase with maximum connection strength, time above threshold, and rate of change. Spectral analysis reveals that the power of nonlinear harmonics and the duration of the oscillations increase as the maximum connection strength and the time above threshold increase. A secondary limit cycle at ∼ 18 Hz, termed a saddle-cycle, is also seen during seizure onset and becomes more prominent and robust with increasing ramp rate. If the time above the threshold is too small, the system does not reach the 10 Hz limit cycle, and only exhibits 18 Hz saddle-cycle oscillations. It is also seen that the time to reach the saturated large amplitude limit-cycle seizure oscillation from both the instability threshold and from the end of the saddle-cycle oscillations is inversely proportional to the square root of the ramp rate.


Assuntos
Córtex Cerebral/fisiologia , Modelos Neurológicos , Convulsões/fisiopatologia , Tálamo/fisiologia , Humanos
20.
J Med Virol ; 92(7): 699-702, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32314810

RESUMO

Neurologic sequelae can be devastating complications of respiratory viral infections. We report the presence of virus in neural and capillary endothelial cells in frontal lobe tissue obtained at postmortem examination from a patient infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Our observations of virus in neural tissue, in conjunction with clinical correlates of worsening neurologic symptoms, pave the way to a closer understanding of the pathogenic mechanisms underlying central nervous system involvement by SARS-CoV-2.


Assuntos
Ageusia/diagnóstico , Ataxia/diagnóstico , Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Transtornos do Olfato/diagnóstico , Pneumonia Viral/diagnóstico , Convulsões/diagnóstico , Idoso , Ageusia/complicações , Ageusia/fisiopatologia , Ageusia/virologia , Ataxia/complicações , Ataxia/fisiopatologia , Ataxia/virologia , Betacoronavirus/genética , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Células Endoteliais/patologia , Células Endoteliais/virologia , Evolução Fatal , Lobo Frontal/irrigação sanguínea , Lobo Frontal/patologia , Lobo Frontal/virologia , Hospitalização , Humanos , Pulmão/irrigação sanguínea , Pulmão/patologia , Pulmão/virologia , Masculino , Neurônios/patologia , Neurônios/virologia , Transtornos do Olfato/complicações , Transtornos do Olfato/fisiopatologia , Transtornos do Olfato/virologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Convulsões/complicações , Convulsões/fisiopatologia , Convulsões/virologia
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