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1.
Artigo em Russo | MEDLINE | ID: mdl-39435771

RESUMO

Electrical stimulation mapping using depth stereo-EEG electrodes is an important method in the structure of presurgical diagnostics in patients with drug-resistant forms of epilepsy. Electrical stimulation mapping was first used in the 1960s and has been actively developed since then, but despite such a long history, a unified protocol for the use of this technique has not been developed and different approaches to stimulation mapping are used in different countries. Based on publications on the topic in PubMed and other available resources, we tried to briefly outline the current opinion on the significance of this technique, paying special attention to the methodological approaches of different schools to stimulation parameters when mapping epileptogenic zones, highlighting in a separate section approaches to stimulation of functionally significant zones Finally, we summarize data on the effectiveness of this method in the presurgical diagnostics of epilepsy.


Assuntos
Epilepsia Resistente a Medicamentos , Eletroencefalografia , Humanos , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/fisiopatologia , Eletroencefalografia/métodos , Mapeamento Encefálico/métodos , Eletrodos , Convulsões/diagnóstico , Convulsões/cirurgia , Convulsões/fisiopatologia , Cuidados Pré-Operatórios/métodos
2.
Front Immunol ; 15: 1459119, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39376559

RESUMO

Background: Focal onset seizures, characterized by localized neuronal hyperexcitability in the brain, can be related to various structural, immune, genetic, or metabolic abnormalities. Autoimmune epilepsies are increasingly recognized. Neurochondrin antibody has been reported in a variety of rare autoimmune neurological disorders. This article aims to highlight the relevance of anti-neurochondrin in autoimmune epilepsy. Methods: This is a case presentation and literature review of autoimmune epilepsy associated with anti-neurochondrin antibody. Case presentation: A 26-year-old African American right-handed man with a history of Sjogren's syndrome presented with near constant, rhythmic left-sided facial twitching movements, and one episode of generalized tonic clonic seizure. Magnetic resonance imaging (MRI) of the brain revealed borderline low volume right hippocampus. Cerebrospinal fluid (CSF) studies yielded elevated protein and mild lymphocytic pleocytosis. Antibody Prevalence in Epilepsy 2 (APE2) score was 6, and autoimmune workup was initiated. Anti-neurochondrin antibody returned positive in the CSF autoimmune encephalitis panel with a titer of 1:512 (Mayo Clinic TEST ID: ENC2). Seizures remained refractory to anti-seizure medications including divalproex, lacosamide, and oxcarbazepine. Immunotherapy with methylprednisolone and immunoglobulin improved his epileptic seizures. Conclusion: This is the first reported case of refractory autoimmune epilepsy with positive CSF anti-neurochondrin antibody. This study contributes to the body of evidence supporting the role of neurochondrin antibody in epilepsy. Considering autoimmune testing in individuals with seizures having APE2 score > 4 can aid in timely diagnosis of immune-mediated epilepsy and initiation of immunotherapy, which can result in favorable clinical outcomes. Diagnosis of autoimmune epilepsy, in most cases, is based on clinical characteristics, MRI results, and CSF findings. In addition to the traditional antibody panel for autoimmune encephalitis, some novel antibodies, such as anti-neurochondrin, should also be considered.


Assuntos
Autoanticorpos , Humanos , Masculino , Adulto , Autoanticorpos/líquido cefalorraquidiano , Autoanticorpos/imunologia , Convulsões/etiologia , Convulsões/tratamento farmacológico , Convulsões/imunologia , Proteínas do Tecido Nervoso/imunologia , Imageamento por Ressonância Magnética
3.
J Assoc Physicians India ; 72(10): e37-e38, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39390881

RESUMO

Majority of the eclampsia or preeclampsia occur between 20 weeks of gestation and within 48 hours postpartum. Postpartum eclampsia usually occurs on a background of preeclampsia. Late postpartum eclampsia (LPE) without preeclampsia is a rarity. LPE with posterior reversible encephalopathy syndrome (PRES) and mild hypertension is extremely rare. We report a case of LPE with PRES without preeclampsia, at a blood pressure of 140/90 mm Hg. Seizures occurring late postpartum period could be due to LPE and this can occur even with mild hypertension.


Assuntos
Eclampsia , Período Pós-Parto , Humanos , Feminino , Gravidez , Eclampsia/diagnóstico , Eclampsia/fisiopatologia , Adulto , Síndrome da Leucoencefalopatia Posterior/diagnóstico , Síndrome da Leucoencefalopatia Posterior/fisiopatologia , Transtornos Puerperais/diagnóstico , Transtornos Puerperais/etiologia , Pressão Sanguínea/fisiologia , Convulsões/etiologia , Convulsões/diagnóstico
4.
Acta Neurobiol Exp (Wars) ; 84(3): 266-274, 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39392022

RESUMO

Evidence is provided that the glycosylated flavonoid vitexin (apigenin­8­C­beta­D­glucopyranoside) attenuates pentylenetetrazole (PTZ)­induced acute tonic­clonic seizures in rats. However, the effects of chronic and systemic vitexin in PTZ­kindled rats remain unknown. The aim of this work was to investigate the effect of long­term treatment with vitexin in the PTZ­kindling model of epilepsy. Male Wistar rats received intraperitoneal injections of PTZ at a subconvulsive dose of 35 mg/kg every other day for 29 days. Either saline containing dimethyl sulfoxide - DMSO 1%  (vehicle), diazepam (2 mg/kg; positive control) or vitexin (2.5 mg/kg) was administered intraperitoneally 30 min before each PTZ injection. The behavioral reactions were recorded by 30 min immediately after each PTZ injection. Furthermore, on the 31st day, that is, 48 h after the latter dose of PTZ, the animals were euthanized and renal and hepatic biochemical markers were evaluated in blood serum. Chronic treatment with either diazepam or vitexin attenuated the seizures provoked by PTZ injections. Neither diazepam nor vitexin caused changes in renal levels of creatinine and urea and in hepatic levels of aspartate aminotransferase and alanine aminotransferase. Our findings suggest that chronic administration of vitexin attenuates the progression of PTZ­induced kindling without causing side effects on kidneys and liver.


Assuntos
Anticonvulsivantes , Apigenina , Diazepam , Excitação Neurológica , Pentilenotetrazol , Ratos Wistar , Convulsões , Animais , Masculino , Apigenina/farmacologia , Anticonvulsivantes/farmacologia , Excitação Neurológica/efeitos dos fármacos , Diazepam/farmacologia , Convulsões/tratamento farmacológico , Convulsões/induzido quimicamente , Modelos Animais de Doenças , Ratos , Fatores de Tempo , Convulsivantes/toxicidade , Epilepsia/tratamento farmacológico , Epilepsia/induzido quimicamente
5.
J Vis Exp ; (211)2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39400191

RESUMO

Complementary metal-oxide-semiconductor high-density microelectrode array (CMOS-HD-MEA) systems can record neurophysiological activity from cell cultures and ex vivo brain slices in unprecedented electrophysiological detail. CMOS-HD-MEAs were first optimized to record high-quality neuronal unit activity from cell cultures but have also been shown to produce quality data from acute retinal and cerebellar slices. Researchers have recently used CMOS-HD-MEAs to record local field potentials (LFPs) from acute, cortical rodent brain slices. One LFP of interest is seizure-like activity. While many users have produced brief, spontaneous epileptiform discharges using CMOS-HD-MEAs, few users reliably produce quality seizure-like activity. Many factors may contribute to this difficulty, including electrical noise, the inconsistent nature of producing seizure-like activity when using submerged recording chambers, and the limitation that 2D CMOS-MEA chips only record from the surface of the brain slice. The techniques detailed in this protocol should enable users to consistently induce and record high-quality seizure-like activity from acute brain slices with a CMOS-HD-MEA system. In addition, this protocol outlines the proper treatment of CMOS-HD-MEA chips, the management of solutions and brain slices during experimentation, and equipment maintenance.


Assuntos
Microeletrodos , Convulsões , Animais , Convulsões/fisiopatologia , Encéfalo/fisiologia , Semicondutores , Camundongos , Ratos , Metais/química , Óxidos/química
6.
PLoS One ; 19(10): e0299964, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39388428

RESUMO

BACKGROUND: Anti-seizure medications (ASMs) are the primary therapeutic mode to control seizures in patients with epilepsy. Adherence to the medications is critical to achieving the goals of epilepsy therapy. However, the cost of the medications and the interrupted availability of ASMs contribute to non-adherence to epilepsy treatment. Therefore, this study aimed to assess ASM adherence and its association with self-reported medication availability and affordability. OBJECTIVE: To assess whether self-reported availability and affordability of Anti-seizure medications affect medication adherence among Epileptic Patients at Eka Kotebe General Hospital, Addis Ababa, Ethiopia, from January 13, 2023 to March 23, 2023. METHODS: A hospital-based analytical cross-sectional study was conducted among 357 epileptic patients using the Consecutive sampling method in Eka Kotebe General Hospital, Addis Ababa, Ethiopia. ASM adherence was measured using a self-report 3items questionnaire focusing on medication use patterns of patients from their last visit to the current visit. Statistical packages for Social Sciences 26.0 version statistical software cleaned, coded and analyzed the collected data. Binary logistic regression was fitted, and P-values less than 0.05 were considered to have statistical significance. RESULT: The prevalence of ASM adherence was 55.2% with 95% CI (50.1%; 60.2%). About two-thirds (61.3%) of patients in this study had limited access to the ASMs or could not afford the medications. Self-reported availability of ASMs (AOR = 2.01, 95% CI = 1.01, 3.98) was significantly associated with ASM adherence. Self-reported affordability of ASMs was associated with ASM adherence in the Bivariate logistic regression analysis; however, when adjusted for other covariates in the multivariable logistic regression, no significant association was observed (p = 0.674). CONCLUSION AND RECOMMENDATION: Only about half of the epileptic patients adhered to ASMs at Eka Kotebe General Hospital. Self-reported availability of ASMs was an essential factor. Improving access to ASMs is critical to improving adherence and management of epilepsy.


Assuntos
Anticonvulsivantes , Epilepsia , Adesão à Medicação , Autorrelato , Humanos , Etiópia , Feminino , Masculino , Adulto , Adesão à Medicação/estatística & dados numéricos , Estudos Transversais , Epilepsia/tratamento farmacológico , Epilepsia/economia , Anticonvulsivantes/uso terapêutico , Anticonvulsivantes/economia , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Inquéritos e Questionários , Convulsões/tratamento farmacológico , Convulsões/economia
7.
BMJ Case Rep ; 17(10)2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39414323

RESUMO

A male baby born out of consanguineous marriage (third degree) to a primigravida mother presented to our hospital on day 21 of life as his third hospitalisation with jerky movements, respiratory distress and refusal to feed. The baby had blood culture-positive sepsis, which was treated adequately. He was given antiseizure therapy for jerky movements, but there was no response to multiple antiseizure therapy, and then pyridoxine was added. A significant response was noted with the addition of clonazepam. Neuroimaging and electroencephalogram were normal. The whole exome sequencing suggested a homozygous mutation (frameshift variant c.97delA in exon 2 of the GLRB gene) associated with hyperekplexia 2, resulting in the amino acid substitution p.Lys34fs*27.


Assuntos
Homozigoto , Hiperecplexia , Humanos , Masculino , Recém-Nascido , Hiperecplexia/genética , Hiperecplexia/diagnóstico , Hiperecplexia/tratamento farmacológico , Clonazepam/uso terapêutico , Convulsões/genética , Convulsões/tratamento farmacológico , Convulsões/diagnóstico , Diagnóstico Diferencial , Receptores de Glicina/genética , Anticonvulsivantes/uso terapêutico , Mutação , Consanguinidade
8.
BMC Psychiatry ; 24(1): 687, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39407178

RESUMO

BACKGROUND: Electroconvulsive therapy (ECT) is an important treatment for several severe psychiatric conditions, yet its precise mechanism of action remains unknown. Increased inhibition in the brain after ECT seizures, mediated by γ-aminobutyric acid (GABA), has been linked to clinical effectiveness. Case series on epileptic patients report a postictal serum concentration increase of the GABAA receptor agonist allopregnanolone. Serum allopregnanolone remains unchanged after a full ECT series, but possible transient effects directly after a single ECT seizure remain unexplored. The primary aim was to measure serum concentrations of allopregnanolone and its substrate progesterone after one ECT seizure. Secondary aims were to examine whether concentrations at baseline, or postictal changes, either correlate with seizure generalization or predict clinical outcome ratings after ECT. METHODS: A total of 130 participants (18-85 years) were included. Generalization parameters comprised peak ictal heart rate, electroencephalographic (EEG) seizure duration, and prolactin increase. Outcome measures were ratings of clinical global improvement, perceived health status and subjective memory impairment. Non-parametric tests were used for group comparisons and correlations. The prediction analyses were conducted with binary logistic and simple linear regression analyses. RESULTS: Allopregnanolone and progesterone remained unchanged and correlated neither with seizure generalization nor with clinical outcome. In men (n = 50), progesterone increased and allopregnanolone change correlated negatively with EEG seizure duration. In a subgroup analysis (n = 62), higher baseline allopregnanolone and progesterone correlated with postictal EEG suppression. CONCLUSIONS: ECT seizures have different physiologic effects than generalized seizures in epilepsy. Progesterone might have implications for psychiatric illness in men.


Assuntos
Eletroconvulsoterapia , Pregnanolona , Progesterona , Convulsões , Humanos , Pregnanolona/sangue , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Eletroconvulsoterapia/métodos , Convulsões/sangue , Convulsões/terapia , Progesterona/sangue , Adolescente , Adulto Jovem , Idoso de 80 Anos ou mais , Resultado do Tratamento , Eletroencefalografia , Estudos de Coortes
9.
Sci Rep ; 14(1): 24756, 2024 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-39433766

RESUMO

Rapid sub-nanometer neuronal deformations have been shown to occur as a consequence of action potentials in vitro, allowing for optical registration of discrete axonal and synaptic depolarizations. Such optically-measured deformations are a novel signature for recording neural activity. We demonstrate this signature can be extended to in vivo measurements through recording of rapid neuronal deformations on the population level with holographic, optical phase-based recordings. Our system demonstrates, for the first time, non-invasive recordings of in vivo tissue deformation associated with population level neuronal activity, including through-skull. We confirmed this technique across a range of neural activation models, including direct epidural focal electrical stimulation, anesthetic-induced cortical deactivation, activation of primary somatosensory cortex via whisker barrel stimulation, and pharmacologically-induced seizures. Collectively, we show holographic imaging provides a pathway for high-resolution, label-free, non-invasive recording of transcranial in vivo neural activity at depth, making it highly advantageous for studying neural function and signaling.


Assuntos
Neurônios , Imagem Óptica , Córtex Somatossensorial , Animais , Córtex Somatossensorial/fisiologia , Córtex Somatossensorial/diagnóstico por imagem , Imagem Óptica/métodos , Neurônios/fisiologia , Potenciais de Ação/fisiologia , Estimulação Elétrica , Holografia/métodos , Masculino , Camundongos , Ratos , Convulsões/fisiopatologia , Convulsões/diagnóstico por imagem
10.
BMC Cardiovasc Disord ; 24(1): 582, 2024 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-39438824

RESUMO

BACKGROUND: The impact of air bubbles into the cerebral circulation after open heart surgery has been a topic of discussion since the introduction of the heart-lung machine. The aim of the study was to evaluate whether the use of a dedicated commercial sponge diffuser is better than a custom-made narrow section cannula or the absence of CO2 in preventing neurological events after aortic valve replacement via J mini-sternotomy. METHODS: Three cohorts of J-shaped mini-sternotomy performed at three different centers were prospectively compared: CO2 supplied via sponge diffuser, CO2 supplied via cannula, and no CO2 supply. Propensity matching was used to obtain comparable groups. The primary endpoints were postoperative stroke, transitory ischemic attack, convulsions, and dizziness. Secondary endpoints were 30-day mortality, duration of mechanical ventilation, and intensive care unit length of stay. RESULTS: 275 patients were enrolled in the study. After propensity matching, the sponge diffuser cohort had a significantly lower duration of mechanical ventilation (P < 0.001) and 30-day mortality (P = 0.05) when compared to the cannula cohort and the no-CO2 cohort, a lower incidence of all neurological events (P = 0.03) and dizziness (P = 0.05) when compare to the no-CO2 cohort, and a lower intensive care unit length of stay when compared to the cannula cohort (P = 0.001). CONCLUSIONS: The sponge diffuser used to deliver the CO2 into the surgical field during aortic valve replacement via J mini-sternotomy has been demonstrated to guarantee better neurological outcomes compared to a custom-made narrow section cannula or the absence of CO2.


Assuntos
Dióxido de Carbono , Implante de Prótese de Valva Cardíaca , Esternotomia , Humanos , Masculino , Feminino , Idoso , Resultado do Tratamento , Estudos Prospectivos , Esternotomia/efeitos adversos , Fatores de Tempo , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/instrumentação , Implante de Prótese de Valva Cardíaca/mortalidade , Fatores de Risco , Respiração Artificial , Idoso de 80 Anos ou mais , Cânula , Tempo de Internação , Desenho de Equipamento , Valva Aórtica/cirurgia , Valva Aórtica/fisiopatologia , Ataque Isquêmico Transitório/etiologia , Ataque Isquêmico Transitório/prevenção & controle , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/etiologia , Convulsões/etiologia , Convulsões/prevenção & controle , Embolia Aérea/prevenção & controle , Embolia Aérea/etiologia , Pessoa de Meia-Idade , Circulação Cerebrovascular , Itália
11.
Pharmacol Res Perspect ; 12(6): e70026, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39439218

RESUMO

One third of epilepsy patients are resistant to treatment with current anti-seizure medications. The ketogenic diet is used to treat some forms of refractory epilepsy, but the mechanism of its action has not yet been elucidated. In this study, we aimed to investigate whether the hydroxycarboxylic acid receptor 2 (HCA2), a known immunomodulatory receptor, plays a role in mediating the protective effect of this diet. We demonstrate for the first time that selective agonists at this receptor can directly reduce seizures in animal models. Agonists also reduce network activity in rodent and human brain slices. Ketogenic diet is known to increase circulating levels of endogenous HCA2 agonists, and we show that the effect of ketogenic diet in reducing seizures in the 6 Hz seizure model is negated in HCA2-deficient mice. Our data support the potential of HCA2 as a target for the treatment of epilepsy and potentially for neurodegenerative diseases.


Assuntos
Dieta Cetogênica , Epilepsia , Camundongos Knockout , Receptores Acoplados a Proteínas G , Animais , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Camundongos , Epilepsia/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Convulsões/prevenção & controle , Convulsões/metabolismo , Ratos , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Anticonvulsivantes/administração & dosagem
12.
Epilepsy Res ; 207: 107457, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39388981

RESUMO

OBJECTIVE: To evaluate the recurrence risk following a first unprovoked seizure using both single-factor and multiple-factor approaches, as well as to further analyze the potential risk factors associated with recurrence. METHODS: In a prospective cohort study, a total of 201 individuals who experienced their initial unprovoked seizure were recruited from January 2010 to December 2019. The cumulative recurrence rates were calculated by Kaplan-Meier survival curves. Multivariate analyses for recurrence risk were conducted utilizing the Cox regression model. Additionally, interaction effects were evaluated by quantifying the attributable proportion due to interaction (AP). RESULTS: The cumulative recurrence rates were as follows: 29.4 % at 6 months, 35.8 % at 1 year, 41.1 % at 2 years, 47.9 % at 5 years, and 57.5 % at 10 years. Notably, the majority of recurrences, specifically 61.2 %, manifested within the initial 6 months following the onset, with 74.4 % occurring within the first year, and 82.6 % within the initial 2 years. The recurrence risk of patients with epileptic abnormal discharges on VEEG, nocturnal seizure, abnormal MRI, prior brain insult and focal seizure was 71.9 %, 61.4 %, 61.5 %, 75.0 %, and 69.7 %, respectively. Epileptiform discharges (RR 2.5, 95 % CI 1.4-4.3, P=0.001) and prior brain insult (RR 2.1, 95 % CI 1.2-3.7, P=0.007) were predictors of recurrence. Interaction analysis showed the combination of epileptiform discharges and prior brain insult was associated with a 7-fold increased risk of recurrence (RR 7.0, 95 %CI 3.5-14.2),with AP estimated at 0.34, the combination of epileptiform discharges and nocturnal seizure was associated with a 4-fold increased risk of recurrence(RR 4.3, 95 %CI 2.4-7.4), with AP estimated at -0.25,and the combination of prior brain insult and nocturnal seizures was associated with a 4-fold increased risk of recurrence(RR 4.1, 95 %CI 1.9-8.9), with AP estimated at -0.03. CONCLUSIONS: Patients with epileptiform discharges VEEG, nocturnal seizures, abnormal MRI findings, prior brain insult, or focal seizures exhibited a substantial recurrence rate. Specifically, the presence of epileptiform discharges in VEEG recordings, and a history of prior brain insult were identified as independent risk factors associated with recurrence following an initial unprovoked seizure. Notably, individuals with multiple risk factors exhibited a significantly higher recurrence risk compared to those with no or a single risk factor.


Assuntos
Recidiva , Convulsões , Humanos , Masculino , Feminino , Fatores de Risco , Estudos Prospectivos , Adulto , Adolescente , Adulto Jovem , Eletroencefalografia , Pessoa de Meia-Idade , Estudos de Coortes , Imageamento por Ressonância Magnética , Criança
13.
Actas Esp Psiquiatr ; 52(5): 616-624, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39403909

RESUMO

BACKGROUND: Functional/dissociative seizures (FDS), also known as psychogenic non-epileptic seizures (PNES), are sudden, transient, and involuntary events that include motor, sensory, cognitive or autonomic function alterations. In this work we analyzed the psychopathological characteristics of a subgroup of women who suffer from FDS with the aim to analyze the role of psychological trauma, with special emphasis on trauma due to sexual abuse (SA). METHODS: Forty-five women diagnosed with FDS were included in the study (age range 18 to 64 years, mean = 34.7, standard deviation (SD) = 13.1). Clinical and psychopathological characteristics were reviewed. All patients have completed the clinical interviews, the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID II) and the Global Assessment of Functioning (GAF) according to a special protocol for mental health assessment. Also, the history of sexual abuse trauma, the history of other non-sexual traumas and absence of history of trauma were reviewed. RESULTS: Eighty percent of the cases reported a history of trauma, and 40% reported a history of SA. Patients with a history of SA presented a significantly lower average age of seizure onset than patients with a history of other non-sexual traumas (p = 0.021). Significant associations were found between SA and post-traumatic stress disorder (PTSD) (p = 0.031), and SA and history of suicide attempts (p = 0.037). CONCLUSIONS: SA carries serious implications for the mental health of women suffering from FDS. Mental health professionals must consider the history of this type of trauma to provide the necessary care for this patient population.


Assuntos
Transtornos Dissociativos , Convulsões , Transtornos de Estresse Pós-Traumáticos , Humanos , Feminino , Adulto , Transtornos de Estresse Pós-Traumáticos/psicologia , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Convulsões/psicologia , Transtornos Dissociativos/psicologia , Delitos Sexuais/psicologia
14.
PLoS Genet ; 20(10): e1011428, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39405291

RESUMO

Börjeson-Forssman-Lehmann syndrome (BFLS) is an X-linked intellectual disability and endocrine disorder caused by pathogenic variants of plant homeodomain finger gene 6 (PHF6). An understanding of the role of PHF6 in vivo in the development of the mammalian nervous system is required to advance our knowledge of how PHF6 mutations cause BFLS. Here, we show that PHF6 protein levels are greatly reduced in cells derived from a subset of patients with BFLS. We report the phenotypic, anatomical, cellular and molecular characterization of the brain in males and females in two mouse models of BFLS, namely loss of Phf6 in the germline and nervous system-specific deletion of Phf6. We show that loss of PHF6 resulted in spontaneous seizures occurring via a neural intrinsic mechanism. Histological and morphological analysis revealed a significant enlargement of the lateral ventricles in adult Phf6-deficient mice, while other brain structures and cortical lamination were normal. Phf6 deficient neural precursor cells showed a reduced capacity for self-renewal and increased differentiation into neurons. Phf6 deficient cortical neurons commenced spontaneous neuronal activity prematurely suggesting precocious neuronal maturation. We show that loss of PHF6 in the foetal cortex and isolated cortical neurons predominantly caused upregulation of genes, including Reln, Nr4a2, Slc12a5, Phip and ZIC family transcription factor genes, involved in neural development and function, providing insight into the molecular effects of loss of PHF6 in the developing brain.


Assuntos
Deficiência Intelectual Ligada ao Cromossomo X , Proteínas Repressoras , Convulsões , Animais , Feminino , Humanos , Masculino , Camundongos , Calcinose/genética , Calcinose/patologia , Calcinose/metabolismo , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Modelos Animais de Doenças , Face/anormalidades , Dedos/anormalidades , Hipogonadismo/genética , Hipogonadismo/patologia , Hipogonadismo/metabolismo , Deficiência Intelectual/genética , Deficiência Intelectual Ligada ao Cromossomo X/genética , Deficiência Intelectual Ligada ao Cromossomo X/patologia , Camundongos Knockout , Células-Tronco Neurais/metabolismo , Obesidade , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Convulsões/genética , Convulsões/metabolismo , Transcrição Gênica , Doenças Vestibulares/genética , Doenças Vestibulares/patologia
15.
Pharmacogenet Genomics ; 34(9): 285-290, 2024 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-39356102

RESUMO

AIMS: To investigate the association of CYP2C9 metabolic phenotypes with phenytoin plasma concentration ([PTH]) in neurosurgical patients from the Brazilian Public Health System. METHODS: Patients (n = 170) were treated with phenytoin (300 mg/day) perioperatively as prophylaxis for postoperative seizures. Two to 10 days after surgery, a blood sample was collected for quantification of [PTH] and genotyping of CYP2C9*2 and *3 alleles. CYP2C9 metabolic phenotypes, NM (normal), IM (intermediate), and PM (poor) metabolizer, were inferred from CYP2C9 diplotypes. Linear regression modeling was applied to identify predictors of [PTH]. RESULTS: Wide (22-fold) interindividual variation in [PTH] was observed (2.2-47.5 mg/l). [PTH] associated significantly (Kruskal-Wallis P < 0.005) with CYP2C9 phenotypes and there was a significant trend (Jonckheere-Terpstra test, P < 0.0001) for [PTH] increase in the order NM < IM < PM. [PTH] was within the target therapeutic range (10-20 mg/l) in 34.7% of patients, while 39.4% and 25.9% had [PTH] below and above the range, respectively. CYP2C9 phenotypes associated significantly (chi-square P = 0.004) with the distribution of patients in [PHT] therapeutic categories and the Cramér's V test pointed to moderate magnitude of the effect of CYP2C9 phenotypes (V = 0.211). CONCLUSION: Diplotype-predicted CYP2C9 metabolic phenotypes are associated significantly with [PTH] in neurosurgical Brazilian patients receiving phenytoin for postsurgery seizure prophylaxis. [PHT] increased progressively in the phenotype order NM < IM < PM, and all PM patients had [PHT] above the target therapeutic range, consistent with the CPIC guideline 'strong' recommendation for phenytoin dosing adjustments in PMs.


Assuntos
Anticonvulsivantes , Citocromo P-450 CYP2C9 , Fenótipo , Fenitoína , Humanos , Citocromo P-450 CYP2C9/genética , Fenitoína/sangue , Fenitoína/administração & dosagem , Fenitoína/farmacocinética , Brasil , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/sangue , Anticonvulsivantes/administração & dosagem , Idoso , Convulsões/tratamento farmacológico , Convulsões/genética , Procedimentos Neurocirúrgicos/efeitos adversos , Adolescente , Genótipo , Adulto Jovem
16.
Rev Fac Cien Med Univ Nac Cordoba ; 81(3): 598-607, 2024 09 27.
Artigo em Espanhol | MEDLINE | ID: mdl-39352843

RESUMO

Introduction: porphyria is a rare condition in which heme metabolism is altered. Clinical case: 29-year-old young man who goes to the emergency room with abdominal pain, vomiting and seizures. To determine the underlying cause, a brain computed tomography (CT) and magnetic resonance imaging (MRI) were performed, confirming the presence of involvement at the parieto-occipital level. Laboratory and urine tests are positive for porphyria, with improvement and resolution of the condition through targeted treatment. Discussion: Porphyrias are rare metabolic disorders with dominant autonomic inheritance that affect heme biosynthesis. In a minority of cases, an external factor can trigger a crisis producing abdominal and neurological symptoms. Imaging findings in acute porphyria are characteristic of PRES (posterior reversible encephalopathy syndrome), with cortico-subcortical involvement. Conclusion: Although it is an uncommon etiology in typical PRES imaging, acute porphyria attacks should be suspected in young patients with seizure attacks without hypertension and associated abdominal pain.


Introducción: La porfiria, es una afección poco común en  la que se encuentra alterado el metabolismo del grupo hemo. Caso clínico: joven de 29 años que acude a urgencias por dolor abdominal, vómitos y convulsiones. Para determinar la causa subyacente, se llevó a cabo una tomografía computarizada (TC) y resonancia magnética (RM) cerebral, que confirma la presencia de afectación a nivel parietooccipital. Las pruebas de laboratorio y de orina resultan positivas para porfiria, con mejoría y resolución del cuadro mediante tratamiento dirigido. Discusión: Las porfirias son trastornos metabólicos poco comunes con herencia autonómica dominante que afectan a la biosíntesis del grupo hemo. En una minoría de los casos, un factor externo puede desencadenar una crisis produciendo sintomatología abdominal y neurológica. Los hallazgos en imagen en cuadros de porfiria aguda son característicos de PRES (síndrome de encefalopatía posterior reversible), con afectación córtico-subcortical. Conclusión: Aunque se trata de una etiología infrecuente en imagen característica de PRES, las crisis de porfiria aguda deben sospecharse en pacientes jóvenes con crisis convulsivas sin hipertensión y cuadro de dolor abdominal asociado.


Assuntos
Imageamento por Ressonância Magnética , Porfiria Aguda Intermitente , Síndrome da Leucoencefalopatia Posterior , Tomografia Computadorizada por Raios X , Humanos , Masculino , Adulto , Porfiria Aguda Intermitente/complicações , Porfiria Aguda Intermitente/diagnóstico , Síndrome da Leucoencefalopatia Posterior/etiologia , Convulsões/etiologia , Dor Abdominal/etiologia
18.
Sci Rep ; 14(1): 23782, 2024 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-39390030

RESUMO

Mitochondrial calcium overload plays an important role in the neurological insults in seizure. The Rab7 GTPase-activating protein, Tre-2/Bub2/Cdc16 domain family member 15 (TBC1D15), is involved in the regulation of mitochondrial calcium dynamics by mediating mitochondria-lysosome membrane contact. However, whether TBC1D15-regulated mitochondria-lysosome membrane contact and mitochondrial calcium participate in neuronal injury in seizure is unclear. We aimed to investigate the effect of TBC1D15-regulated mitochondria-lysosome membrane contact on epileptiform discharge-induced neuronal damage and further explore the underlying mechanism. Lentiviral vectors (Lv) infection and stereotaxic adeno-associated virus (AAV) injection were used to regulate TBC1D15 expression before establishing in vitro epileptiform discharge and in vivo status epilepticus (SE) models. TBC1D15's effect on inter-organellar interactions, mitochondrial calcium levels and neuronal injury in seizure was evaluated. The results showed that abnormalities in mitochondria-lysosome membrane contact, mitochondrial calcium overload, mitochondrial dysfunction, increased levels of reactive oxygen species, and prominent neuronal damage were partly relieved by TBC1D15 overexpression, whereas TBC1D15 knockdown markedly deteriorated these phenomena. Further examination revealed that epileptiform discharge-induced mitochondrial calcium overload in primary hippocampal neurons was closely associated with abnormal mitochondria-lysosome membrane contact. This study highlights the crucial role played by TBC1D15-regulated mitochondria-lysosome membrane contact in epileptiform discharge-induced neuronal injury by alleviating mitochondrial calcium overload.


Assuntos
Cálcio , Proteínas Ativadoras de GTPase , Lisossomos , Mitocôndrias , Neurônios , Convulsões , Animais , Mitocôndrias/metabolismo , Cálcio/metabolismo , Proteínas Ativadoras de GTPase/metabolismo , Proteínas Ativadoras de GTPase/genética , Lisossomos/metabolismo , Convulsões/metabolismo , Neurônios/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , Ratos , Espécies Reativas de Oxigênio/metabolismo , Ratos Sprague-Dawley , Modelos Animais de Doenças , Membranas Intracelulares/metabolismo , Estado Epiléptico/metabolismo , Estado Epiléptico/patologia
19.
Ideggyogy Sz ; 77(9-10): 329-338, 2024 Sep 30.
Artigo em Húngaro | MEDLINE | ID: mdl-39352258

RESUMO

Background and purpose:

Combined epilepsy (with generalized and focal seizures) is a recently accepted and yet underreported epilepsy type. We intended to review the literature of combined epilepsy and to report the individual findings of the 31 combined epilepsy patients in our database. Thereafter, we investigated the characteristics of the patients at the group level.

. Methods:

The individual findings of the 31 patients were tabulated. We characterized the group with special reference to epide­miology, timing and the sequence of gene­ralized and focal seizures, family history of seizures and severity of the electro-clinical phenotype. The variables were compared to those of the generalized epilepsy and the focal epilepsy groups of our database. We carried out statistical analyses by the two-sided Fishers’s exact test and the Kruskal-Wallis and post-hoc Dunn tests.

. Results:

The prevalence of combined epilepsy was 1.56% within the total sample of the classifiable epilepsy patients. Females were affected more often than males (67.7% and 32.3%, respectively). Statistically significant associations emerged firstly between the “short interval” subgroup (where the generalized and focal seizures occurred with short time difference) and the lack of other cerebral abnormality, and secondly between the “long interval” subgroup (where 4 to 37 years elapsed between the occurrence of the two seizure types) and the presence of other brain abnormality (p = 0.02). The proportion of patients with positive family history of seizures was greater in the combined epilepsy- than in the generalized epilepsy group (p = 0.03) and the focal epilepsy group (p < 0.0001) of the database. The electro-clinical phenotype of the absence seizures showed more atypical findings (indicating poor prognosis) in combined epilepsy than in the generalized absence epilepsy patients of the database (p < 0,0001). Despite dissimilar patient selection and study design, our main findings were in accord with those of prior studies. The dissection of the combined epilepsy group into the “long interval” and “short interval” subgroups was a novel approach that highlighted the dissimilar pathogenetic and clinical correlates of each.

. Conclusion:

The case reports might facilitate the spread of information about combined epilepsy in the medical community. Analyses of the patients at the group level resulted in clinically useful pieces of evidence.

.


Assuntos
Epilepsias Parciais , Epilepsia Generalizada , Convulsões , Humanos , Eletroencefalografia , Prevalência , Convulsões/epidemiologia
20.
J Transl Med ; 22(1): 895, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39367475

RESUMO

BACKGROUND: Epilepsy is a prevalent neurological disorder in which seizures cause recurrent episodes of unconsciousness or muscle convulsions, seriously affecting the patient's work, quality of life, and health and safety. Timely prediction of seizures is critical for patients to take appropriate therapeutic measures. Accurate prediction of seizures remains a challenge due to the complex and variable nature of EEG signals. The study proposes an epileptic seizure model based on a multidimensional Transformer with recurrent neural network(LSTM-GRU) fusion for seizure classification of EEG signals. METHODOLOGY: Firstly, a short-time Fourier transform was employed in the extraction of time-frequency features from EEG signals. Second, the extracted time-frequency features are learned using the Multidimensional Transformer model. Then, LSTM and GRU are then used for further learning of the time and frequency characteristics of the EEG signals. Next, the output features of LSTM and GRU are spliced and categorized using the gating mechanism. Subsequently, seizure prediction is conducted. RESULTS: The model was tested on two datasets: the Bonn EEG dataset and the CHB-MIT dataset. On the CHB-MIT dataset, the average sensitivity and average specificity of the model were 98.24% and 97.27%, respectively. On the Bonn dataset, the model obtained about 99% and about 98% accuracy on the binary classification task and the tertiary upper classification task, respectively. CONCLUSION: The findings of the experimental investigation demonstrate that our model is capable of exploiting the temporal and frequency characteristics present within EEG signals.


Assuntos
Eletroencefalografia , Epilepsia , Redes Neurais de Computação , Convulsões , Humanos , Eletroencefalografia/métodos , Convulsões/fisiopatologia , Convulsões/diagnóstico , Epilepsia/fisiopatologia , Epilepsia/diagnóstico , Processamento de Sinais Assistido por Computador , Análise de Fourier
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