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2.
Neurology ; 102(9): e209348, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38608210

RESUMO

BACKGROUND AND OBJECTIVES: Medicaid beneficiaries in many American academic medical centers can receive care in a separate facility than those not covered by Medicaid. We aimed to identify possible disparities in care by evaluating the association between facility type (integrated faculty practice or Medicaid-only outpatient clinic) and telehealth utilization in people with epilepsy. METHODS: We performed retrospective analyses using structured data from the Mount Sinai Health System electronic medical record data from January 2003 to August 2021. We identified people of all ages with epilepsy who were followed by an epileptologist after January 3, 2018, using a validated ICD-9-CM/10-CM coded case definition. We evaluated associations between practice setting and telehealth utilization, an outcome measure that captures the evolving delivery of neurologic care in a post-coronavirus disease 2019 era, using multivariable logistic regression. RESULTS: We identified 4,586 people with epilepsy seen by an epileptologist, including Medicaid beneficiaries in the Medicaid outpatient clinic (N = 387), Medicaid beneficiaries in the faculty practice after integration (N = 723), and non-Medicaid beneficiaries (N = 3,476). Patients not insured by Medicaid were significantly older (average age 40 years vs 29 in persons seen in Medicaid-only outpatient clinic and 28.5 in persons insured with Medicaid seen in faculty practice [p < 0.0001]). Medicaid beneficiaries were more likely to have drug-resistant epilepsy (DRE), with 51.94% of people seen in Medicaid-only outpatient clinic, 41.63% of Medicaid beneficiaries seen in faculty practice, and 37.2% of non-Medicaid beneficiaries having DRE (p < 0.0001). Medicaid outpatient clinic patients were less likely to have telehealth visits (phone or video); 81.65% of patients in the Medicaid outpatient clinic having no telehealth visits vs 71.78% of Medicaid beneficiaries in the faculty practice and 70.89% of non-Medicaid beneficiaries (p < 0.0001). In an adjusted logistic regression analysis, Medicaid beneficiaries had lower odds (0.61; 95% CI 0.46-0.81) of using teleneurology compared with all patients seen in faculty practice (p = 0.0005). DISCUSSION: Compared with the Medicaid-only outpatient clinic, we found higher telehealth utilization in the integrated faculty practice with no difference by insurance status (Medicaid vs other). Integrated care may be associated with better health care delivery in people with epilepsy; thus, future research should examine its impact on other epilepsy-related outcomes.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Equidade em Saúde , Estados Unidos , Humanos , Adulto , Medicaid , Estudos Retrospectivos , Epilepsia/epidemiologia , Epilepsia/terapia
3.
Lakartidningen ; 1212024 Apr 08.
Artigo em Sueco | MEDLINE | ID: mdl-38591842

RESUMO

The Swedish national guidelines for epilepsy stipulate regular health care contacts in the years following diagnosis, referral for epilepsy surgery in cases of pharmacoresistant epilepsy, multidisciplinary teams, and adequate patient information particularly for women of childbearing age. The last years have seen advances in many research areas of relevance for the basic epilepsy care, and Sweden has contributed regarding pharmacotherapy, seizure-related risks, sudden unexpected death in epilepsy (SUDEP), and digital tools. An increasing prevalence of epilepsy and stagnating or decreasing health care resources makes nationwide implementation of this knowledge challenging and increases the risk of unequal access to care. Innovation and focus on prioritized groups, such as newly diagnosed and persons with pharmacoresistant epilepsy or comorbidities, will be needed.


Assuntos
Morte Súbita , Epilepsia , Humanos , Feminino , Prevalência , Morte Súbita/epidemiologia , Epilepsia/epidemiologia , Epilepsia/terapia , Convulsões , Comorbidade , Fatores de Risco
4.
BMC Med Inform Decis Mak ; 24(1): 101, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637746

RESUMO

BACKGROUND: The effective management of epilepsy in women of child-bearing age necessitates a concerted effort from multidisciplinary teams. Nevertheless, there exists an inadequacy in the seamless exchange of knowledge among healthcare providers within this context. Consequently, it is imperative to enhance the availability of informatics resources and the development of decision support tools to address this issue comprehensively. MATERIALS AND METHODS: The development of the Women with Epilepsy of Child-Bearing Age Ontology (WWECA) adhered to established ontology construction principles. The ontology's scope and universal terminology were initially established by the development team and subsequently subjected to external evaluation through a rapid Delphi consensus exercise involving domain experts. Additional entities and attribute annotation data were sourced from authoritative guideline documents and specialized terminology databases within the respective field. Furthermore, the ontology has played a pivotal role in steering the creation of an online question-and-answer system, which is actively employed and assessed by a diverse group of multidisciplinary healthcare providers. RESULTS: WWECA successfully integrated a total of 609 entities encompassing various facets related to the diagnosis and medication for women of child-bearing age afflicted with epilepsy. The ontology exhibited a maximum depth of 8 within its hierarchical structure. Each of these entities featured three fundamental attributes, namely Chinese labels, definitions, and synonyms. The evaluation of WWECA involved 35 experts from 10 different hospitals across China, resulting in a favorable consensus among the experts. Furthermore, the ontology-driven online question and answer system underwent evaluation by a panel of 10 experts, including neurologists, obstetricians, and gynecologists. This evaluation yielded an average rating of 4.2, signifying a positive reception and endorsement of the system's utility and effectiveness. CONCLUSIONS: Our ontology and the associated online question and answer system hold the potential to serve as a scalable assistant for healthcare providers engaged in the management of women with epilepsy (WWE). In the future, this developmental framework has the potential for broader application in the context of long-term management of more intricate chronic health conditions.


Assuntos
Epilepsia , Informática , Feminino , Humanos , Epilepsia/terapia , Bases de Dados Factuais , Gerenciamento de Dados , China
5.
Stem Cell Res Ther ; 15(1): 108, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38637847

RESUMO

BACKGROUND: Epilepsy affects ∼60 million people worldwide. Most antiseizure medications in the market act on voltage-gated sodium or calcium channels, indirectly modulating neurotransmitter GABA or glutamate levels or multiple targets. Earlier studies made significant efforts to directly deliver GABA into the brain with varied success. Herein, we have hypothesized to directly deliver exogenous GABA to the brain with epilepsy through extracellular vesicles (EVs) from human GABA-producing cells and their progenitors as EVs largely mimic their parent cell composition. METHODS: Human neural stem cells (NSCs), medial ganglionic eminence (MGE) cells, and GABAergic interneurons (INs) were generated from induced pluripotent stem cells (iPSCs) and characterized. EVs were isolated from NSCs, MGE cells, and INs and characterized for size and distribution, morphological features, and molecular markers. Exogenous GABA was passively loaded to the isolated EVs as a zwitterion at physiological pH, and the encapsulated dose of GABA was quantified. Epilepsy was developed through status epilepticus induction in Fisher rats by administration of repeated low doses of kainic acid. The extent of the seizures was measured for 10 h/ day for 3-6 months by video recording and its evaluation for stage III, IV and V seizures as per Racine scale. EVs from INs, MGE cells, and NSCs encapsulated with exogenous GABA were sequentially tested in the 4th, 5th, and 6th months by intranasal administration in the rats with epilepsy for detailed seizure, behavioral and synapse analysis. In separate experiments, several controls including exogenic GABA alone and EVs from INs and MGE cells were evaluated for seizure-controlling ability. RESULTS: Exogenic GABA could enter the brain through EVs. Treatment with EVs from INs and MGE cells encapsulated with GABA significantly reduced total seizures, stage V seizures, and total time spent in seizure activity. EVs from NSCs encapsulated with GABA demonstrated limited seizure control. Exogenic GABA alone and EVs from INs and MGE cells individually failed to control seizures. Further, exogenic GABA with EVs from MGE cells improved depressive behavior while partially improving memory functions. Co-localization studies confirmed exogenous GABA with presynaptic vesicles in the hippocampus, indicating the interaction of exogenous GABA in the brain with epilepsy. CONCLUSION: For the first time, the study demonstrated that exogenous GABA could be delivered to the brain through brain cell-derived EVs, which could regulate seizures in temporal lobe epilepsy. It is identified that the cellular origin of EVs plays a vital role in seizure control with exogenous GABA.


Assuntos
Epilepsia do Lobo Temporal , Epilepsia , Vesículas Extracelulares , Humanos , Ratos , Animais , Convulsões/tratamento farmacológico , Epilepsia/terapia , Epilepsia do Lobo Temporal/tratamento farmacológico , Ácido gama-Aminobutírico/farmacologia
6.
Ital J Pediatr ; 50(1): 77, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641843

RESUMO

BACKGROUND: Epilepsy is a chronic neurological disorder that is more likely to be diagnosed in children. The main treatment involves long-term use of anti-epileptic drugs and above all, home care is of great importance. As there has not been a widely accepted home care protocols, simulating a home care environment is necessary for caregivers to develop skills of proper home care. This study aims to evaluate the effectiveness of a simulation training of family management style (STOFMS) for parents of children with epilepsy in China. METHODS: A randomized controlled trial was conducted on 463 children with epilepsy and their families. They were recruited from March 2020 to November 2022 and randomly assigned to the STOFMS group or the conventional group in a 1:1 ratio. Scores of family management measures, 8-item of Morisky Medication Adherence and epilepsy clinical symptom of both groups were collected at three points of time: within 24 h after admission (T0), 3 months after discharge (T1), and 6 months after discharge (T2). Changes due to intervention were compared across groups by repeated-measures ANOVA. The study report followed the CONSORT 2010 checklist. RESULTS: There were statistically significant differences between the two groups at T2. A considerable increase over the baseline was observed in the total management level score and subscale scores in the STOFMS group at T1, compared with essentially no change in the control group. In terms of medication adherence, the STOFMS group performance improved greatly at T1 and T2 compared with the control group. The same result was also found in clinical efficacy at T2 (p < 0.05). CONCLUSION: STOFMS is an effective intervention to improve family management level, treatment adherence and clinical efficacy for children with epilepsy. TRIAL REGISTRATION: The registration number is ChiCTR2200065128. Registered at 18 October 2022, http://www.medresman.org.cn.


Assuntos
Epilepsia , Serviços de Assistência Domiciliar , Treinamento por Simulação , Criança , Humanos , Pais/educação , Epilepsia/terapia , Cuidadores
7.
Lancet Neurol ; 23(5): 511-521, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38631767

RESUMO

Epilepsy diagnosis is often delayed or inaccurate, exposing people to ongoing seizures and their substantial consequences until effective treatment is initiated. Important factors contributing to this problem include delayed recognition of seizure symptoms by patients and eyewitnesses; cultural, geographical, and financial barriers to seeking health care; and missed or delayed diagnosis by health-care providers. Epilepsy diagnosis involves several steps. The first step is recognition of epileptic seizures; next is classification of epilepsy type and whether an epilepsy syndrome is present; finally, the underlying epilepsy-associated comorbidities and potential causes must be identified, which differ across the lifespan. Clinical history, elicited from patients and eyewitnesses, is a fundamental component of the diagnostic pathway. Recent technological advances, including smartphone videography and genetic testing, are increasingly used in routine practice. Innovations in technology, such as artificial intelligence, could provide new possibilities for directly and indirectly detecting epilepsy and might make valuable contributions to diagnostic algorithms in the future.


Assuntos
Inteligência Artificial , Epilepsia , Humanos , Longevidade , Epilepsia/terapia , Convulsões/diagnóstico , Comorbidade
8.
Lancet ; 403(10433): 1208-1209, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38461836
9.
Lancet ; 403(10433): 1254-1266, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38461840

RESUMO

BACKGROUND: Mental health difficulties are common in children and young people with chronic health conditions, but many of those in need do not access evidence-based psychological treatments. The study aim was to evaluate the clinical effectiveness of integrated mental health treatment for children and young people with epilepsy, a common chronic health condition known to be associated with a particularly high rate of co-occurring mental health difficulties. METHODS: We conducted a parallel group, multicentre, open-label, randomised controlled trial of participants aged 3-18 years, attending epilepsy clinics across England and Northern Ireland who met diagnostic criteria for a common mental health disorder. Participants were randomised (1:1; using an independent web-based system) to receive the Mental Health Intervention for Children with Epilepsy (MICE) in addition to usual care, or assessment-enhanced usual care alone (control). Children and young people in both groups received a full diagnostic mental health assessment. MICE was a modular psychological intervention designed to treat common mental health conditions in children and young people using evidence-based approaches such as cognitive behaviour therapy and behavioural parenting strategies. Usual care for mental health disorders varied by site but typically included referral to appropriate services. Participants, along with their caregivers, and clinicians were not masked to treatment allocation but statisticians were masked until the point of analysis. The primary outcome, analysed by modified intention-to-treat, was the parent-report Strengths and Difficulties Questionnaire (SDQ) at 6 months post-randomisation. The study is complete and registered with ISRCTN (57823197). FINDINGS: 1401 young people were potentially deemed eligible for study inclusion. Following the exclusion of 531 young people, 870 participants were assessed for eligibility and completed the SDQ, and 480 caregivers provided consent for study inclusion between May 20, 2019, and Jan 31, 2022. Between Aug 28, 2019, and Feb 21, 2022, 334 participants (mean ages 10·5 years [SD 3·6] in the MICE group vs 10·3 [4·0] in control group at baseline) were randomly assigned to an intervention using minimisation balanced by age, primary mental health disorder, diagnosis of intellectual disability, and autistic spectrum disorder at baseline. 168 (50%) of the participants were female and 166 (50%) were male. 166 participants were randomly assigned to the MICE group and 168 were randomly assigned to the control group. At 6 months, the mean SDQ difficulties for the 148 participants in the MICE group was 17·6 (SD 6·3) and 19·6 (6·1) for the 148 participants in the control group. The adjusted effect of MICE was -1·7 (95% CI -2·8 to -0·5; p=0·0040; Cohen's d, 0·3). 14 (8%) patients in the MICE group experienced at least one serious adverse event compared with 24 (14%) in the control group. 68% percent of serious adverse events (50 events) were admission due to seizures. INTERPRETATION: MICE was superior to assessment-enhanced usual care in improving symptoms of emotional and behavioural difficulties in young people with epilepsy and common mental health disorders. The trial therefore shows that mental health comorbidities can be effectively and safely treated by a variety of clinicians, utilising an integrated intervention across ages and in the context of intellectual disability and autism. The evidence from this trial suggests that such a model should be fully embedded in epilepsy services and serves as a model for other chronic health conditions in young people. FUNDING: UK National Institute for Health Research Programme Grants for Applied Research programme and Epilepsy Research UK Endeavour Project Grant.


Assuntos
Epilepsia , Deficiência Intelectual , Adolescente , Criança , Feminino , Humanos , Masculino , Análise Custo-Benefício , Inglaterra , Epilepsia/terapia , Saúde Mental , Intervenção Psicossocial , Resultado do Tratamento , Pré-Escolar
10.
Curr Opin Neurol ; 37(2): 97-98, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38451481
12.
Cell Mol Neurobiol ; 44(1): 27, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38443733

RESUMO

Epilepsy, a prevalent neurological disorder characterized by high morbidity, frequent recurrence, and potential drug resistance, profoundly affects millions of people globally. Understanding the microscopic mechanisms underlying seizures is crucial for effective epilepsy treatment, and a thorough understanding of the intricate neural circuits underlying epilepsy is vital for the development of targeted therapies and the enhancement of clinical outcomes. This review begins with an exploration of the historical evolution of techniques used in studying neural circuits related to epilepsy. It then provides an extensive overview of diverse techniques employed in this domain, discussing their fundamental principles, strengths, limitations, as well as their application. Additionally, the synthesis of multiple techniques to unveil the complexity of neural circuits is summarized. Finally, this review also presents targeted drug therapies associated with epileptic neural circuits. By providing a critical assessment of methodologies used in the study of epileptic neural circuits, this review seeks to enhance the understanding of these techniques, stimulate innovative approaches for unraveling epilepsy's complexities, and ultimately facilitate improved treatment and clinical translation for epilepsy.


Assuntos
Epilepsia , Humanos , Epilepsia/terapia , Convulsões
13.
Epilepsy Behav ; 153: 109717, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428173

RESUMO

AIMS: To evaluate the knowledge, attitudes, and practical skills of students submitted to a 6-week intensive training in epilepsy compared to students without any training but mandatory neurology classes. METHODS: It is a case-control study. After completing a 6-week intensive Academic, Clinical, and Research Program in epilepsy, TUMSs answered a validated Knowledge Attitudes and Practices (KAP) questionnaire. The control group, composed of undergraduate students who shared the same age, academic year, and compulsory hours for learning about epilepsy as TUMSs, was also assessed through the KAP instrument. Answers from both groups were submitted to Fisher exact and the χ2 test to observe differences among groups. Descriptive statistics were also performed. RESULTS: TUMSs displayed better results in theoretical knowledge such as the definition and causes of epilepsy, and the application of paraclinical studies essential for diagnosing epilepsy. From their perspective, people with epilepsy encounter restricted opportunities for preserving their social life and employment and they are more prone to workplace accidents. They are convinced that facing epilepsy presents a notable risk due to the difficulties linked with diagnosis, considering epilepsy a challenging disease for general practitioners to identify and follow up. Likewise, they exhibited improvement in treatment adjustment and treatment monitoring of patients with epilepsy, mainly in pregnancy cases. Finally, they had greater knowledge about what to do when they witness a person experiencing a seizure. CONCLUSION: Our study showed that a 6-week intensive education program in epilepsy increased the knowledge and practical skills and changed the attitude toward patients with epilepsy of undergraduate students.


Assuntos
Epilepsia , Estudantes de Medicina , Humanos , Estudos de Casos e Controles , Epilepsia/terapia , Convulsões , Escolaridade , Inquéritos e Questionários , Conhecimentos, Atitudes e Prática em Saúde
14.
Epilepsy Behav ; 153: 109721, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428175

RESUMO

OBJECTIVES: This study aimed to translate and validate the Vietnamese version of the Epilepsy Self-Management Scale (V-ESMS). METHODS: The translation and cross-cultural adaptation of the original version of the ESMS into Vietnamese followed the Principles of Good Practice for the Translation and Cultural Adaptation Process for Patient-Reported Outcomes Measures guideline with "forward-backward" translation and culturally adapted. The participants were recruited consecutively at neurology clinics at Nguyen Tri Phuong Hospital and University Medical Center, Ho Chi Minh City, from January 2022 to July 2022 and required to complete the V-ESMS. The validity was assessed by exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Cronbach's alpha and intraclass correlation coefficient (ICC) were used to evaluate internal and temporal reliability, respectively. RESULTS: A total of 200 participants were recruited for analysis. The V-ESMS included 36 items and five domains. The factor loading ranged between 0.313 and 0.927; most items loaded in their hypothesized factors proved in the original scale. Using the CFA, theCMIN/DF, comparative fit index, and root mean square error of approximation were 2.883, 0.80, and 0.097, respectively. The Cronbach's alpha in each domain was 0.79-0.907; the scale was 0.936. The ICC from 0.94 to 0.98 showed excellent test-retest reliability. CONCLUSION: The 36-item V-ESMS with five domains presented good validity and reliability. This instrument could be used to assess self-management in people with epilepsy in Vietnam.


Assuntos
Epilepsia , Autogestão , Humanos , Vietnã , Inquéritos e Questionários , Reprodutibilidade dos Testes , Epilepsia/terapia , Psicometria
15.
Epilepsia ; 65(4): 873-886, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38305763

RESUMO

The current pace of development and applications of large language models (LLMs) is unprecedented and will impact future medical care significantly. In this critical review, we provide the background to better understand these novel artificial intelligence (AI) models and how LLMs can be of future use in the daily care of people with epilepsy. Considering the importance of clinical history taking in diagnosing and monitoring epilepsy-combined with the established use of electronic health records-a great potential exists to integrate LLMs in epilepsy care. We present the current available LLM studies in epilepsy. Furthermore, we highlight and compare the most commonly used LLMs and elaborate on how these models can be applied in epilepsy. We further discuss important drawbacks and risks of LLMs, and we provide recommendations for overcoming these limitations.


Assuntos
Inteligência Artificial , Epilepsia , Humanos , Registros Eletrônicos de Saúde , Epilepsia/diagnóstico , Epilepsia/terapia , Idioma
16.
Epilepsy Res ; 201: 107315, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38364765

RESUMO

PURPOSE: Epilepsy is a debilitating disease that can lead to series of social and psychological issues, impairing the quality of life of people with epilepsy (PWE). This survey aimed to investigate the awareness, attitudes, and first-aid knowledge of epilepsy in university students METHOD: This cross-sectional study was conducted in Henan Province, China between January 1 and April 30, 2022. Students majored in education, medicine, science and engineering from 8 universities attended the study. The survey questionnaire comprised 28 questions covering 4 sections: demographic characteristics, awareness of epilepsy, attitudes toward PWE and knowledge of first aid for seizures. RESULTS: A total of 2376 university students completed the questionnaire. 94.7% heard of epilepsy. In the first aid knowledge section, individual question was correctly answered by at least 50% students, 9.3% students correctly answered all questions. Attitude toward PWE was independently (R2 =0.108, F=73.227, p < 0.001) associated with both awareness of epilepsy (B=0.411, p < 0.001) and first aid knowledge of epilepsy (B=0.047, p = 0.001). Among the three majors, medical students had more positive attitudes toward PWE than students majored in education, science and engineering (p < 0.05). However, medical students performed worse among the groups when answering the first aid knowledge questions. CONCLUSION: This survey showed that university students in Central China had a good awareness of epilepsy. For medical students, improvements are necessary for the awareness of the first aid knowledge for seizure.


Assuntos
Epilepsia , Primeiros Socorros , Humanos , Estudos Transversais , Universidades , Qualidade de Vida , Conhecimentos, Atitudes e Prática em Saúde , Epilepsia/terapia , Epilepsia/psicologia , Convulsões , Estudantes/psicologia , Inquéritos e Questionários , China
17.
Neurology ; 102(4): e208087, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38306606

RESUMO

The National Association of Epilepsy Centers first published the guidelines for epilepsy centers in 1990, which were last updated in 2010. Since that update, epilepsy care and the science of guideline development have advanced significantly, including the importance of incorporating a diversity of stakeholder perspectives such as those of patients and their caregivers. Currently, despite extensive published data examining the efficacy of treatments and diagnostic testing for epilepsy, there remain significant gaps in data identifying the essential services needed for a comprehensive epilepsy center and the optimal manner for their delivery. The trustworthy consensus-based statements (TCBS) process produces unbiased, scientifically valid guidelines through a transparent process that incorporates available evidence and expert opinion. A systematic literature search returned 5937 relevant studies from which 197 articles were retained for data extraction. A panel of 41 stakeholders with diverse expertise evaluated this evidence and drafted recommendations following the TCBS process. The panel reached consensus on 52 recommendations covering services provided by specialized epilepsy centers in both the inpatient and outpatient settings in major topic areas including epilepsy monitoring unit care, surgery, neuroimaging, neuropsychology, genetics, and outpatient care. Recommendations were informed by the evidence review and reflect the consensus of a broad panel of expert opinions.


Assuntos
Epilepsia , Humanos , Epilepsia/diagnóstico , Epilepsia/terapia , Consenso , Neuroimagem
18.
Int J Biol Macromol ; 263(Pt 2): 130468, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38417757

RESUMO

Epilepsy is a medical disorder marked by sporadic seizures accompanied by alterations in consciousness. The molecular mechanisms responsible for epilepsy and the factors contributing to alterations in neuronal structure compromised apoptotic responses in neurons, and disturbances in regeneration pathways in glial cells remain unidentified. MicroRNAs (miRNAs) are short noncoding RNA that consist of a single strand. They typically contain 21 to 23 nucleotides. miRNAs participate in the process of RNA silencing and the regulation of gene expression after transcription by selectively binding to mRNA molecules that possess complementary sequences. The disruption of miRNA regulation has been associated with the development of epilepsy, and manipulating a single miRNA can impact various cellular processes, hence serving as a potent intervention approach. Despite existing obstacles in the delivery and safety of miRNA-based treatments, researchers are actively investigating the potential of miRNAs to operate as regulators of brain activity and as targets for treating and preventing epilepsy. Hence, the utilization of miRNA-based therapeutic intervention shows potential for future epilepsy management. The objective of our present investigation was to ascertain the involvement of miRNAs in the causation and advancement of epilepsy. Moreover, they have undergone scrutiny for their potential utilization in therapeutic intervention.


Assuntos
Epilepsia , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/uso terapêutico , MicroRNAs/metabolismo , Epilepsia/genética , Epilepsia/terapia , Epilepsia/metabolismo , Interferência de RNA , RNA Mensageiro/metabolismo , Neurônios/metabolismo
19.
Pediatr Neurol ; 153: 48-55, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38320458

RESUMO

BACKGROUND: Neonatal seizures caused by hypoxic-ischemic encephalopathy (HIE) have significant morbidity and mortality. There is variability in clinical practice regarding treatment duration with antiseizure medication (ASM) after resolution of provoked neonatal seizures. We examined epilepsy incidence and developmental outcomes in post-HIE neonates discharged or not on ASM. METHODS: We conducted a retrospective chart review of all HIE-admitted neonates to the University of Iowa Hospitals & Clinics neonatal intensive care unit between January 2008 and February 2021 who presented with encephalopathy, underwent therapeutic hypothermia, and developed seizures. Neonates were divided into two groups depending on whether ASM was continued or discontinued on discharge. We evaluated the incidence of epilepsy and developmental outcomes on follow-up in these two cohorts up to 12 months. RESULTS: Sixty-nine neonates met the study criteria. ASM was continued on discharge in 41 neonates (59%) and discontinued before discharge in 28 (41%). At the 12-month follow-up, nine neonates (13%) had a diagnosis of epilepsy, out of which seven neonates had ASM continued on discharge (odds ratio [OR]: 2.84; 95% confidence interval [CI]: 0.48, 29.9)]. There was no statistical difference between the development of postneonatal epilepsy between the two groups (P value 0.29). There was no significant difference in developmental outcome between the two groups after adjusting for covariates like magnetic resonance imaging (MRI) brain abnormality and number of seizure days (OR: 0.68; 95% CI: 0.21, 2.22; P = 0.52). CONCLUSION: We found no significant risk of seizure recurrence by age 12 months in infants who had discontinued ASM before discharge compared with those who had continued ASM. There was no difference in developmental outcomes at the 12-month follow-up between groups after adjusting for brain MRI abnormality and the number of seizure days during admission. Our results support early discontinuation of ASM after resolution of acute provoked seizures in neonates with HIE.


Assuntos
Epilepsia , Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Doenças do Recém-Nascido , Recém-Nascido , Lactente , Humanos , Estudos Retrospectivos , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Hipóxia-Isquemia Encefálica/epidemiologia , Hipóxia-Isquemia Encefálica/diagnóstico , Incidência , Epilepsia/terapia , Convulsões/tratamento farmacológico , Convulsões/epidemiologia , Convulsões/etiologia , Hipotermia Induzida/métodos , Doenças do Recém-Nascido/terapia
20.
Nat Commun ; 15(1): 1249, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341419

RESUMO

Lateral hypothalamic (LH) hypocretin/orexin neurons (HONs) control brain-wide electrical excitation. Abnormally high excitation produces epileptic seizures, which affect millions of people and need better treatments. HON population activity spikes from minute to minute, but the role of this in seizures is unknown. Here, we describe correlative and causal links between HON activity spikes and seizures. Applying temporally-targeted HON recordings and optogenetic silencing to a male mouse model of acute epilepsy, we found that pre-seizure HON activity predicts and controls the electrophysiology and behavioral pathology of subsequent seizures. No such links were detected for HON activity during seizures. Having thus defined the time window where HONs influence seizures, we targeted it with LH deep brain stimulation (DBS), which inhibited HON population activity, and produced seizure protection. Collectively, these results uncover a feature of brain activity linked to seizures, and demonstrate a proof-of-concept treatment that controls this feature and alleviates epilepsy.


Assuntos
Epilepsia , Convulsões , Camundongos , Animais , Masculino , Humanos , Orexinas/genética , Convulsões/prevenção & controle , Epilepsia/genética , Epilepsia/terapia , Neurônios/fisiologia , Hipotálamo
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