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1.
Autoimmun Rev ; 18(10): 102367, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31404705

RESUMO

Aggregation of immuno-proteomic data reveals that i) herpesviruses and synaptic proteins -in particular Synapsin-1 and Bassoon - share a large number of hexapeptides that also recur in hundreds of epitopes experimentally validated as immunopositive in the human host, and ii) the shared peptides are also spread among human epilepsy-related proteins. The data indicate that cross-reactive processes may be associated with pathogenetic mechanisms in epilepsy, thus suggesting a role of autoimmunity in etiopathology of epilepsies after herpesvirus-infections.


Assuntos
Autoimunidade/imunologia , Epilepsia/etiologia , Epitopos/imunologia , Herpes Simples/complicações , Herpesviridae/imunologia , Fragmentos de Peptídeos/imunologia , Sinapsinas/imunologia , Animais , Reações Cruzadas , Epilepsia/patologia , Herpes Simples/imunologia , Humanos
2.
Cell Mol Life Sci ; 76(16): 3207-3228, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31172215

RESUMO

Matrix metalloproteinases (MMPs) are a group of over twenty proteases, operating chiefly extracellularly to cleave components of the extracellular matrix, cell adhesion molecules as well as cytokines and growth factors. By virtue of their expression and activity patterns in animal models and clinical investigations, as well as functional studies with gene knockouts and enzyme inhibitors, MMPs have been demonstrated to play a paramount role in many physiological and pathological processes in the brain. In particular, they have been shown to influence learning and memory processes, as well as major neuropsychiatric disorders such as schizophrenia, various kinds of addiction, epilepsy, fragile X syndrome, and depression. A possible link connecting all those conditions is either physiological or aberrant synaptic plasticity where some MMPs, e.g., MMP-9, have been demonstrated to contribute to the structural and functional reorganization of excitatory synapses that are located on dendritic spines. Another common theme linking the aforementioned pathological conditions is neuroinflammation and MMPs have also been shown to be important mediators of immune responses.


Assuntos
Aprendizagem , Metaloproteinases da Matriz/metabolismo , Memória/fisiologia , Transtornos Mentais/patologia , Animais , Encéfalo/metabolismo , Epilepsia/metabolismo , Epilepsia/patologia , Humanos , Metaloproteinases da Matriz/genética , Transtornos Mentais/metabolismo , Plasticidade Neuronal , Inibidores Teciduais de Metaloproteinases/genética , Inibidores Teciduais de Metaloproteinases/metabolismo
3.
Cell Mol Life Sci ; 76(16): 3055-3081, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31236626

RESUMO

'A disintegrin and metalloproteases' (ADAMs) are a family of transmembrane proteins with diverse functions in multicellular organisms. About half of the ADAMs are active metalloproteases and cleave numerous cell surface proteins, including growth factors, receptors, cytokines and cell adhesion proteins. The other ADAMs have no catalytic activity and function as adhesion proteins or receptors. Some ADAMs are ubiquitously expressed, others are expressed tissue specifically. This review highlights functions of ADAMs in the mammalian nervous system, including their links to diseases. The non-proteolytic ADAM11, ADAM22 and ADAM23 have key functions in neural development, myelination and synaptic transmission and are linked to epilepsy. Among the proteolytic ADAMs, ADAM10 is the best characterized one due to its substrates Notch and amyloid precursor protein, where cleavage is required for nervous system development or linked to Alzheimer's disease (AD), respectively. Recent work demonstrates that ADAM10 has additional substrates and functions in the nervous system and its substrate selectivity may be regulated by tetraspanins. New roles for other proteolytic ADAMs in the nervous system are also emerging. For example, ADAM8 and ADAM17 are involved in neuroinflammation. ADAM17 additionally regulates neurite outgrowth and myelination and its activity is controlled by iRhoms. ADAM19 and ADAM21 function in regenerative processes upon neuronal injury. Several ADAMs, including ADAM9, ADAM10, ADAM15 and ADAM30, are potential drug targets for AD. Taken together, this review summarizes recent progress concerning substrates and functions of ADAMs in the nervous system and their use as drug targets for neurological and psychiatric diseases.


Assuntos
Proteínas ADAM/metabolismo , Sistema Nervoso/metabolismo , Proteínas ADAM/química , Animais , Transporte Biológico , Epilepsia/metabolismo , Epilepsia/patologia , Humanos , Inflamação/metabolismo , Inflamação/patologia , Bainha de Mielina/fisiologia , Sistema Nervoso/crescimento & desenvolvimento , Canais de Potássio/metabolismo , Proteólise
4.
Paediatr Drugs ; 21(4): 283-290, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31179531

RESUMO

BACKGROUND: A pharmaceutical grade formulation of cannabidiol (CBD) has been approved for the treatment of Dravet syndrome and Lennox-Gastaut syndrome; however, this formulation is not yet available to patients outside the USA. In addition, CBD is thought to have broad anti-seizure properties that may be beneficial for other types of intractable epilepsy. OBJECTIVE: The aim of this study was to evaluate the efficacy, safety and tolerability of artisanal medical CBD oil in patients with developmental and epileptic encephalopathy (DEE) at the tertiary epilepsy center of Bambino Gesù Children's Hospital in Rome, Italy. METHODS: This was a single-center, prospective, open-label study. Patients aged from 1 to 18 years with DEE and seizures refractory to appropriate antiepileptic drugs (AEDs) and other alternative treatments (i.e., vagal nerve stimulator and ketogenic diet) were included. Crystalline extract CBD powder (98-99% pure) in an oil artisanal formulation was added to the baseline AED regimen at a dosage of 2-5 mg/kg/day divided for twice-daily administration, then up-titrated until intolerance or a maximum dosage of 25 mg/kg/day was reached. Patients were treated for at least 6 months. Efficacy, safety and tolerability of CBD treatment were assessed through the evaluation of seizure frequency and reports of adverse effects. RESULTS: Twenty-nine patients were enrolled in this study (41.4% male). The mean duration of exposure to artisanal CBD was 11.2 months [range 6-25 months; standard deviation (SD) ± 4.4 months]. Mean age at study enrollment was 9.3 years (range 1.9-16.3 years; SD ± 4.7 years). Eleven out of 29 patients (37.9%) had a ≥ 50% improvement in seizure frequency; one patient became seizure free. None of the patients reported worsening seizure frequency; however, 18 patients (62.1%) experienced no beneficial effect regarding seizure frequency. Adverse effects were reported in seven patients (24.14%), most commonly somnolence, decreased appetite and diarrhea. Adverse events were mild and transient, and no dose modification of CBD or other AEDs was required. CONCLUSIONS: These data suggest that CBD may have beneficial effects in patients with DEE and an acceptable safety profile. Placebo-controlled randomized trials should be conducted to formally assess the safety and efficacy of CBD in patients with DEE.


Assuntos
Anticonvulsivantes/uso terapêutico , Canabidiol/uso terapêutico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia/tratamento farmacológico , Adolescente , Anticonvulsivantes/farmacologia , Canabidiol/farmacologia , Criança , Pré-Escolar , Epilepsia Resistente a Medicamentos/patologia , Epilepsia/patologia , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos
5.
Paediatr Drugs ; 21(4): 291-301, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31250322

RESUMO

OBJECTIVE: This trial evaluated the short-term safety and tolerability, steady-state pharmacokinetics, and preliminary efficacy of brivaracetam oral solution in children aged 1 month to < 16 years with epilepsy. METHODS: This was a phase IIa, open-label, single-arm, fixed three-step dose escalation trial of 3-weeks duration (N01263; NCT00422422). Patients were taking one to three concomitant antiepileptic drugs. Brivaracetam oral solution dosage, in two divided daily doses, was increased each week: approximately 0.8, 1.6, and 3.2 mg/kg/day for patients aged ≥ 8 years, and 1.0, 2.0, and 4.0 mg/kg/day for patients aged < 8 years. RESULTS: Of the 100 patients enrolled, 90 (90.0%) completed the trial. The safety population comprised 99 patients. Treatment-emergent adverse events (TEAEs) considered drug related by the investigator were reported by 32/99 (32.3%) patients, most commonly (≥ 5%) somnolence (7.1%) and decreased appetite (6.1%). TEAEs were reported by 66/99 (66.7%) patients, most commonly (≥ 5%) convulsion, irritability, pyrexia, somnolence, and decreased appetite. In patients with a history of focal seizures with or without secondary generalization and no primary generalized seizures aged 4 to < 16 years (n = 34), drug-related TEAEs and TEAE incidences were 47.1% and 67.6%, respectively. Steady-state trough brivaracetam and brivaracetam metabolite plasma concentrations increased proportionally with dose. The ≥ 50% responder rates (all seizure types) were 21.3% (all patients, n = 80) and 36.4% (patients with focal seizures, aged 4 to < 16 years, n = 22). CONCLUSIONS: This open-label trial in pediatric patients with epilepsy provides preliminary information that short-term, adjunctive brivaracetam treatment is well tolerated and effective. Plasma concentrations of brivaracetam and metabolites increased with increasing dose.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Pirrolidinonas/uso terapêutico , Adolescente , Anticonvulsivantes/farmacologia , Criança , Pré-Escolar , Epilepsia/patologia , Feminino , Humanos , Lactente , Masculino , Pirrolidinonas/farmacologia , Resultado do Tratamento
6.
Acta Neurol Scand ; 140(3): 184-193, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31102535

RESUMO

OBJECTIVES: To determine the prevalence of epilepsy in children with early-onset mitochondrial diseases (MDs) and to evaluate the epileptic phenotypes and associated features. MATERIALS AND METHODS: Children affected by MD with onset during the first year of life were enrolled. Patients were classified according to their mitochondrial phenotype, and all findings in patients with epilepsy versus patients without were compared. The epileptic features were analyzed. RESULTS: The series includes 129 patients (70 females) with median age at disease onset of 3 months. The median time of follow-up was 5 years. Non-syndromic mitochondrial encephalopathy and pyruvate dehydrogenase complex deficiency were the main mitochondrial diseases associated with epilepsy (P < 0.05). Seizures occurred in 48%, and the presence of epilepsy was significantly associated with earlier age at disease onset, presence of perinatal manifestations, and early detection of developmental delay and regression (P < 0.001). Epileptic encephalopathy (EE) with spasms and EE with prominent focal seizures were the most detected epileptic syndromes (37% and 27.4%). Several seizure types were recorded in 53.2%, with the unusual association of generalized and focal epileptic pattern. Disabling epilepsy was detected in 63% and was associated with early seizure onset, presence of several seizure types, epileptic syndrome featuring EE, and the recurrence of episodes of status epilepticus and epilepsia partialis continua (P < 0.05). CONCLUSIONS: Epilepsy in children with early-onset MD may be a presenting or a prominent symptom in a multisystemic clinical presentation. Epilepsy-related factors could determine a worst seizure outcome, leading to a more severe burned of the disease.


Assuntos
Epilepsia/epidemiologia , Doenças Mitocondriais/epidemiologia , Adolescente , Criança , Pré-Escolar , Epilepsia/etiologia , Epilepsia/patologia , Feminino , Humanos , Lactente , Masculino , Doenças Mitocondriais/complicações , Doenças Mitocondriais/patologia , Fenótipo
7.
Molecules ; 24(8)2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31022879

RESUMO

Epilepsy is a prevalent neurological disorder that was reported to affect about 56 million people in the world. Approximately one-third of the epileptic patients that suffer from seizures do not receive effective medical treatment. The aim of this study was to determine the potential anticonvulsant activities of Baldrinal (BAL) with a mouse model of pilocarpine (PILO)-induced epilepsy. The mice were treated with different doses of BAL or sodium valproate prior to PILO injection. Spontaneous and evoked seizures were evaluated from EEG recordings, and their severity was tested by the Racine scale. In addition, the brain tissues were analyzed for histological changes, and the in situ levels of glutamic acid (Glu) and gamma-aminobutyric acid (GABA) were also measured. Activation of astrocytes in the hippocampus was measured. PILO-treated mice showed a significant increase in Glu levels, which was restored by BAL. In addition, BAL treatment also reduced the rate of seizures in the epileptic mice, and ameliorated the increased levels of NMDAR1, BDNF, IL-1ß and TNF-α. Taken together, BAL has a potential antiepileptic effect, which may be mediated by reducing the inflammatory response in the PILO-induced brain and restoring the balance of GABAergic and glutamatergic neurons.


Assuntos
Encéfalo/efeitos dos fármacos , Epilepsia/tratamento farmacológico , Iridoides/administração & dosagem , Convulsões/tratamento farmacológico , Animais , Anticonvulsivantes/administração & dosagem , Encéfalo/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças , Epilepsia/induzido quimicamente , Epilepsia/patologia , Ácido Glutâmico/metabolismo , Humanos , Camundongos , Pilocarpina/toxicidade , Convulsões/induzido quimicamente , Convulsões/patologia , Ácido gama-Aminobutírico/metabolismo
8.
Molecules ; 24(8)2019 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-31013866

RESUMO

Cannabidiol (CBD) is one of the cannabinoids with non-psychotropic action, extracted from Cannabis sativa. CBD is a terpenophenol and it has received a great scientific interest thanks to its medical applications. This compound showed efficacy as anti-seizure, antipsychotic, neuroprotective, antidepressant and anxiolytic. The neuroprotective activity appears linked to its excellent anti-inflammatory and antioxidant properties. The purpose of this paper is to evaluate the use of CBD, in addition to common anti-epileptic drugs, in the severe treatment-resistant epilepsy through an overview of recent literature and clinical trials aimed to study the effects of the CBD treatment in different forms of epilepsy. The results of scientific studies obtained so far the use of CBD in clinical applications could represent hope for patients who are resistant to all conventional anti-epileptic drugs.


Assuntos
Ansiolíticos/uso terapêutico , Anticonvulsivantes/uso terapêutico , Antipsicóticos/uso terapêutico , Canabidiol/uso terapêutico , Cannabis/química , Epilepsia/tratamento farmacológico , Convulsões/tratamento farmacológico , Ansiolíticos/efeitos adversos , Ansiolíticos/química , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/química , Antipsicóticos/efeitos adversos , Antipsicóticos/química , Canabidiol/efeitos adversos , Canabidiol/química , Ensaios Clínicos como Assunto , Epilepsia/patologia , Epilepsia/fisiopatologia , Humanos , Convulsões/patologia , Convulsões/fisiopatologia
9.
Int J Mol Sci ; 20(8)2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31018519

RESUMO

Epilepsy is a common neurological disorder associated with increased morbidity and mortality. Sudden unexpected death in epilepsy, also known as SUDEP, is the main cause of death in patients with epilepsy. SUDEP has an incidence of 1.2 per 1000 person-years in adults and 0.2 per 1000 person-years in children. SUDEP accounts for 8-17% of deaths in patients with epilepsy. It is commonly associated with a history of generalized tonic-clonic seizures, and its risk may be increased by other factors such as postictal electroencephalographic suppression, prone sleeping position, altered heart rate variability, conduction abnormalities, gender, or antiepileptic medications. Recently, electrocardiograms, electroencephalograms, and imaging markers have helped clinicians stratify SUDEP risk and identify patients in need of close monitoring. However, the pathophysiology of SUDEP is likely multifactorial and still unknown. Improving the knowledge of SUDEP incidence, risk factors, and biomarkers can help design and implement effective prevention strategies.


Assuntos
Morte Súbita/epidemiologia , Epilepsia/genética , Animais , Arritmias Cardíacas/complicações , Arritmias Cardíacas/genética , Arritmias Cardíacas/patologia , Arritmias Cardíacas/fisiopatologia , Morte Súbita/patologia , Epilepsia/epidemiologia , Epilepsia/patologia , Epilepsia/fisiopatologia , Predisposição Genética para Doença , Humanos , Fatores de Risco
10.
Chem Biol Interact ; 307: 223-233, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31018114

RESUMO

OBJECTIVE: The aim of this study is to investigate the role of mircoRNA-200c-3p (miR-200c-3p) on hippocampal neuron injury in epileptic rats through the regulation of the AKT signaling pathway by targeting RECK. METHODS: The epilepsy rat model was induced by intraperitoneal injection of lithium chloride-pilocarpine. Successful modeled rats were injected with miR-200c-3p inhibitors, inhibitors NC, siRNA-negative control (NC) and RECK-siRNA. The astrocyte activation, levels of oxidative stress indexes, contents of inflammatory factors and the AKT signaling pathway-related proteins in hippocampus tissues were evaluated. RESULTS: High expression of miR-200c-3p and low expression of RECK were found in the hippocampus tissues of epileptic rats. Downregulation of miR-200c-3p or upregulation of RECK decreased apoptosis of hippocampal neurons, expression of GFAP, content of MDA and increased the activities of GSH-Px and SOD, decreased expression of TNF-α, IL-1ß and IL-6 as well as expression of p-PI3K/t-PI3K and p-Akt/t-Akt in hippocampus tissues of epileptic rats. CONCLUSION: Our study provides evidence that downregulation of miR-200c-3p reduces damage of hippocampal neurons in epileptic rats by upregulating RECK and inactivating the AKT signaling pathway.


Assuntos
Hipocampo/metabolismo , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Regiões 3' não Traduzidas , Animais , Antagomirs/metabolismo , Apoptose , Modelos Animais de Doenças , Regulação para Baixo , Epilepsia/genética , Epilepsia/patologia , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Hipocampo/patologia , Hipocampo/ultraestrutura , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais , Proteínas Supressoras de Tumor/antagonistas & inibidores , Proteínas Supressoras de Tumor/genética , Regulação para Cima
11.
Eur J Paediatr Neurol ; 23(3): 456-465, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31023627

RESUMO

PURPOSE: We assessed trends in spectrum of candidates, diagnostic algorithm, therapeutic approach and outcome of a pediatric epilepsy surgery program between 2000 and 2017. METHODS: All pediatric patients who underwent curative epilepsy surgery in Motol Epilepsy Center during selected period (n = 233) were included in the study and divided into two groups according to time of the surgery (developing program 2000-2010: n = 86, established program 2011-2017: n = 147). Differences in presurgical, surgical and outcome variables between the groups were statistically analyzed. RESULTS: A total of 264 resections or hemispheric disconnections were performed (including 31 reoperations). In the later epoch median age of candidates decreased. Median duration of disease shortened in patients with temporal lobe epilepsy. Number of patients with non-localizing MRI findings (subtle or multiple lesions) rose, as well as those with epileptogenic zone adjacent to eloquent cortex. There was a trend towards one-step procedures guided by multimodal neuroimaging and intraoperative electrophysiology; long-term invasive EEG was performed in fewer patients. Subdural electrodes for long-term invasive monitoring were almost completely replaced by stereo-EEG. The number of focal resections and hemispherotomies rose over time. Surgeries were more often regarded complete. Histopathological findings of resected tissue documented developing spectrum of candidates. 82.0% of all children were seizure-free two years after surgery; major complications occurred in 4.6% procedures; both groups did not significantly differ in these parameters. CONCLUSION: In the established pediatric epilepsy surgery program, our patients underwent epilepsy surgery at younger age and suffered from more complex structural pathology. Outcomes and including complication rate remained stable.


Assuntos
Epilepsia/patologia , Epilepsia/cirurgia , Hemisferectomia/métodos , Neurologia/tendências , Adolescente , Córtex Cerebral/cirurgia , Criança , Pré-Escolar , Eletroencefalografia/métodos , Feminino , Hemisferectomia/efeitos adversos , Humanos , Masculino , Neuroimagem/métodos , Estudos Retrospectivos , Resultado do Tratamento
12.
Am J Vet Res ; 80(5): 480-489, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31034269

RESUMO

OBJECTIVE: To assess visualization of the intracranial arteries and internal carotid artery (ICA) on 3-D time-of-flight (TOF) magnetic resonance angiography (MRA) images obtained at 1.5 T and to investigate factors that affect the image quality of those arteries in dogs. ANIMALS: 39 dogs with idiopathic epilepsy. PROCEDURES: Each dog underwent 3-D TOF MRA, and 5 pairs of intracranial arteries, the basilar artery, and both ICAs were evaluated. Each artery was assigned an image-quality score on a scale of 0 to 3, where 0 = poor and 3 = excellent. Multivariable regression analysis was used to assess whether age, body weight (BW), serum total cholesterol concentration, intracranial volume (ICV), and mean arterial pressure were significantly associated with the image quality of each vessel. RESULTS: In all dogs, the image-quality score was 2 or 3 for the proximal middle cerebral arteries, basilar artery, and caudal aspect of the caudal communicating arteries. In some dogs, the rostral cerebellar arteries, rostral aspect of the caudal communicating arteries, and middle and rostral aspects of the ICA were poorly visualized. For various arteries, image quality was negatively associated with age and positively associated with BW and ICV. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that 3-D TOF MRA images obtained at 1.5 T did not consistently and clearly delineate the ICA and narrow or peripheral intracranial arteries of dogs; therefore, careful attention is required when such images are assessed. Patient age, BW, and ICV can also affect the image quality of some intracranial arteries on 3-D TOF MRA images. (Am J Vet Res 2019;80:480-489).


Assuntos
Artérias Cerebrais/diagnóstico por imagem , Doenças do Cão/diagnóstico por imagem , Epilepsia/veterinária , Angiografia por Ressonância Magnética/veterinária , Animais , Encéfalo/irrigação sanguínea , Cães , Epilepsia/diagnóstico por imagem , Epilepsia/patologia , Feminino , Imagem Tridimensional/métodos , Imagem Tridimensional/veterinária , Angiografia por Ressonância Magnética/métodos , Masculino
13.
Brain Nerve ; 71(4): 374-379, 2019 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-30988224

RESUMO

Tuberous sclerosis complex (TSC) is an autosomal dominant inherited disorders that is characterized by the systemic hamartomas, along with epilepsy, cognitive impairment and hypopigmented macules. It is caused by genetic mutations in either TSC1 or TSC2 gene which encodes hamartin and tuberin, respectively. As the hamartin-tuberin-complex downregulates the mechanistic/mammalian target of the rapamycin complex1 (mTORC1), dysfunction in either hamartin or tuberin induces the constitutive activation of mTORC1. In fact, almost all the symptoms in TSC are derived from the activation of mTORC1. Therefore, mTORC1 inhibitors improves all the symptoms, including skin lesions and neural symptoms. Among the many symptoms, skin lesions appear earlier than renal or pulmonary lesions and are more specific than neuronal symptoms. Therefore, skin lesions are useful for the diagnosis of TSC. This chapter focuses on the features of skin lesions and mechanistic their potential role in differential diagnosis and therapy including the therapeutic use of mTORC1 inhibitors.


Assuntos
Pele/patologia , Esclerose Tuberosa/diagnóstico , Esclerose Tuberosa/patologia , Diagnóstico Diferencial , Epilepsia/patologia , Hamartoma/patologia , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Esclerose Tuberosa/tratamento farmacológico , Proteína 1 do Complexo Esclerose Tuberosa/genética , Proteína 2 do Complexo Esclerose Tuberosa/genética
14.
Brain Dev ; 41(6): 516-521, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30827788

RESUMO

OBJECTIVE: This study measured the serum carnitine levels in patients with epilepsy and determined the factors contributing to low carnitine levels. METHODS: We measured the serum carnitine levels in 94 consecutive patients with epilepsy, including the free carnitine (FC) and acylcarnitine fractions, using an enzyme cycling method. We defined a low FC as a serum FC level < 36 µmol/L. Age, body mass index (BMI), standard deviation score of BMI (BMI-SDS), use of valproate, cognitive disorder, and feeding problems differed between patients with low and normal FC. In patients taking valproate, the associations of the serum FC level with the platelet count and serum ammonia and amylase levels were analyzed. RESULTS: Univariate analysis showed that a low BMI and BMI-SDS, the use of valproate, and cognitive disorder were more frequent in patients with a low FC. Logistic regression analysis revealed that a low BMI-SDS and cognitive disorders were independently associated with a low FC. Among the patients taking valproate, a low BMI-SDS and age were associated with a low FC. The serum FC and ammonia levels were inversely correlated, whereas no correlation was observed between the serum FC level and platelet count or serum amylase level. CONCLUSION: A low BMI and cognitive disorders were related to a low FC in patients with epilepsy and the serum carnitine levels should be monitored in these patients.


Assuntos
Carnitina/análise , Epilepsia/metabolismo , Ácido Valproico/análise , Adolescente , Índice de Massa Corporal , Carnitina/análogos & derivados , Carnitina/sangue , Criança , Pré-Escolar , Disfunção Cognitiva/metabolismo , Epilepsia/complicações , Epilepsia/patologia , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Ácido Valproico/sangue , Adulto Jovem
15.
Korean J Gastroenterol ; 73(2): 105-108, 2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30845387

RESUMO

Achalasia is a motility disorder of the esophagus that is characterized by loss of ganglionic neurons within the myenteric plexus of the lower esophageal sphincter (LES) resulting in failure of the LES to relax. Clinically this disorder presents with simultaneous dysphagia to solids and liquids, and if left untreated, leads to esophageal dilation, which can give rise to many adverse consequences. Extrinsic compression of respiratory structures is one such consequence, and rarely, cases of tracheal compression secondary to achalasia have been reported. However, cases of extrinsic bronchial compression are yet rarer. Here, we present a case series comprised of two patients with achalasia who presented with extrinsic bronchial compression by a dilated esophagus secondary to achalasia.


Assuntos
Obstrução das Vias Respiratórias/diagnóstico , Acalasia Esofágica/diagnóstico , Adulto , Obstrução das Vias Respiratórias/complicações , Asma/patologia , Endoscopia Gastrointestinal , Epilepsia/patologia , Acalasia Esofágica/etiologia , Esfíncter Esofágico Inferior/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Substâncias/patologia , Tomografia Computadorizada por Raios X
16.
J Med Syst ; 43(5): 121, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30915585

RESUMO

In this paper the EEG signal is analyzed by reconstructing the time series EEG signal in High dimensional Phase Space. The computational complexity in higher dimension is reduced by Principal Component Analysis for the High dimensional Phase Space output. Poincare sectioning is done for the first and second Principal Components (PCs). The intersection points of PCs and the Poincare section are collected and used for features calculation. Two layer of classification is done using SVM as first layer and Naive Bayes as second layer. The proposed methodology is evaluated using the CHB-MIT database for 23 subjects. The results are obtained using different channel combinations of EEG signal and highest of 95.63% accuracy, 95.7% sensitivity and 96.55% specificity is obtained for 12 electrode combinations which include electrodes from parietal and occipital lobes. This infers that most of the subjects have dysfunction in hearing (controlled by parietal) and vision (controlled by occipital) during the time of seizure. This GUI has channel selection option and seizure detection for every channel (23) for every 1 s.


Assuntos
Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Epilepsia/diagnóstico por imagem , Epilepsia/patologia , Processamento de Sinais Assistido por Computador , Máquina de Vetores de Suporte , Teorema de Bayes , Eletroencefalografia/métodos , Epilepsia/diagnóstico , Humanos , Análise de Componente Principal , Sensibilidade e Especificidade
17.
Epilepsy Res ; 152: 67-72, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30909054

RESUMO

NG2 cells are oligodendrocyte progenitor cells, and have been shown to receive synaptic input from pyramidal neurons to generate action potentials. Whether any change of these cells occurs after status epilepticus (SE) and subsequent temporal lobe epilepsy remains unknown. In the present study, the expression of NG2 was investigated in the mouse hippocampus after pilocarpine-induced status epilepticus (PISE). We showed that reactive NG2 cells were significantly increased from 1 day to 2 months after PISE. Double immunofluorescence indicated that few NG2 cells differentiated into neurons and astrocytes after PISE, whereas the number of NG2 cells was increased significantly in the stratum lucidum of CA3 area from 1 day onwards after PISE. Our results suggest that the significantly increased reactive NG2 cells from acute to chronic stage after PISE may be involved in epileptogenesis.


Assuntos
Antígenos/metabolismo , Proliferação de Células/fisiologia , Epilepsia/induzido quimicamente , Epilepsia/patologia , Hipocampo/patologia , Células Precursoras de Oligodendrócitos/patologia , Proteoglicanas/metabolismo , Animais , Antígeno CD11b/metabolismo , Calbindina 2/metabolismo , Calbindinas/metabolismo , Proliferação de Células/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Masculino , Camundongos , Agonistas Muscarínicos/toxicidade , Células Precursoras de Oligodendrócitos/efeitos dos fármacos , Células Precursoras de Oligodendrócitos/metabolismo , Pilocarpina/toxicidade , Fatores de Tempo
18.
Int J Mol Sci ; 20(5)2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30818767

RESUMO

Ionotropic glutamate receptors (iGluRs) mediate the synaptic and metabolic actions of glutamate. These iGluRs are classified within the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type, kainate-type, and N-methyl-d-aspartate (NMDA)-type functional receptor families. The iGluR assemblies are regulated by transcription, alternative splicing, and cytoplasmic post-translational modifications. The iGluR subunit proteins are transported from the endoplasmic reticulum, inserted into the synaptic membranes, and anchored at their action site by different scaffolding and interacting proteins. The functional properties of iGluRs depend on their subunit composition, the amino acid sequence of the protein domains, and the scaffolding proteins in the synaptic membranes. The iGluRs are removed from the membranes by enzymatic action and endocytosis. Hippocampal iGluRs are rearranged through the upregulation and downregulation of the subunits following deafferentation and epileptic seizures. The rearrangement of iGluRs and the alteration of their subunit composition transform neurons into "pathological" cells, determining the further plasticity or pathology of the hippocampal formation. In the present review, we summarize the expression of AMPA, kainate, and NMDA receptor subunits following deafferentation, repeated mild seizures, and status epilepticus. We compare our results to literature descriptions, and draw conclusions as to the reactive plasticity of iGluRs in the hippocampus.


Assuntos
Epilepsia/metabolismo , Epilepsia/patologia , Hipocampo/metabolismo , Hipocampo/patologia , Receptores Ionotrópicos de Glutamato/metabolismo , Animais , Mamíferos/metabolismo
19.
J Neurooncol ; 142(3): 577-586, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30805752

RESUMO

PURPOSE: Awake craniotomy is well-established for tumors resected in eloquent brain areas. Whether awake craniotomy provides improved seizure control in patients with epileptic gliomas has not been well evaluated. This study analyzed the incidence, risk factors and outcome of seizures during and following awake craniotomies for patients presenting with epilepsy and glioma. METHODS: Forty-one patients undergoing awake craniotomies for epileptic gliomas were retrospectively analyzed. Postoperative seizure was defined as either early (postoperative day 7 + before) or late onset (after postoperative day 7). Neurologic function was assessed with modified Rankin Scales (mRS) and seizure outcome was assessed using International League Against Epilepsy (ILAE) classification. Multivariable logistic regression was used for clinical variables associated with postoperative seizures. RESULTS: Three patients (7.3%) had intraoperative seizures however did not fail the awake craniotomies. Mean mRS before and after the awake craniotomies were 2.4 and 2.1, respectively (P = 0.032). Fourteen (34.1%) patients had early seizures, which caused longer hospitalization than those without early seizures (P = 0.03). Surgical resection to isocitrate dehydrogenase 1 (IDH1) mutation tumors, comparing to IDH1 wild type tumors, caused better postoperative seizure control. 6-month late seizure freedom was achieved in 33 patients (80.5%). Early seizure recurrence (odds ratio = 30.75; P = 0.039) and postoperative mRS ≥ 3 (odds ratio = 7.00; P = 0.047) were independent risk factors for late seizures. CONCLUSIONS: Intraoperative seizures could be well-controlled during awake craniotomies. Early postoperative seizures extended hospitalization and strongly predicted late seizure recurrence. Awake craniotomies benefited long-term seizure control in patients with epileptic gliomas.


Assuntos
Craniotomia/métodos , Epilepsia/cirurgia , Glioma/cirurgia , Complicações Intraoperatórias/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Convulsões/prevenção & controle , Vigília , Adulto , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Epilepsia/complicações , Epilepsia/patologia , Feminino , Seguimentos , Glioma/complicações , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
20.
Nat Commun ; 10(1): 707, 2019 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-30755602

RESUMO

Aminoacyl-tRNA synthetases (ARSs) function to transfer amino acids to cognate tRNA molecules, which are required for protein translation. To date, biallelic mutations in 31 ARS genes are known to cause recessive, early-onset severe multi-organ diseases. VARS encodes the only known valine cytoplasmic-localized aminoacyl-tRNA synthetase. Here, we report seven patients from five unrelated families with five different biallelic missense variants in VARS. Subjects present with a range of global developmental delay, epileptic encephalopathy and primary or progressive microcephaly. Longitudinal assessment demonstrates progressive cortical atrophy and white matter volume loss. Variants map to the VARS tRNA binding domain and adjacent to the anticodon domain, and disrupt highly conserved residues. Patient primary cells show intact VARS protein but reduced enzymatic activity, suggesting partial loss of function. The implication of VARS in pediatric neurodegeneration broadens the spectrum of human diseases due to mutations in tRNA synthetase genes.


Assuntos
Epilepsia/genética , Mutação , Valina-tRNA Ligase/genética , Alelos , Anticódon , Criança , Pré-Escolar , Progressão da Doença , Epilepsia/enzimologia , Epilepsia/patologia , Feminino , Predisposição Genética para Doença , Humanos , Estudos Longitudinais , Mutação com Perda de Função , Masculino , Microcefalia/enzimologia , Microcefalia/genética , Modelos Moleculares , Transtornos do Neurodesenvolvimento/enzimologia , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/patologia , Linhagem , Biossíntese de Proteínas , Domínios e Motivos de Interação entre Proteínas , RNA de Transferência/genética , Sequenciamento Completo do Exoma , Sequenciamento Completo do Genoma
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