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1.
Med Arch ; 78(2): 122-126, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38566869

RESUMO

Background: Levetiracetam (LEV) is a broad spectrum second-generation antiepileptic drug (AED). Objective: The objective of the study was to investigate the efficacy and safety of levetiracetam for childhood epilepsies. Methods: This is single, tertiary centre observational, prospective study, that included paediatric patients who were treated with levetiracetam at Paediatric hospital University Clinical Centre Sarajevo, during the period of 15 years (2008-2022). Inclusion criteria were: paediatric patients age > 1 month, diagnosed with epilepsy according to International League Against Epilepsy. After the introduction of levetiracetam, each patient has been followed up at least 12 months. According to the outcome the patients were divided into 5 groups: seizure reduction >50%, seizure reduction <50%, complete seizure freedom, the same number of seizures and increased number of seizures. From these groups two intergroups have been formed: responders (seizure reduction >50% and complete seizure freedom) and non-responders (seizure reduction <50%, the same number of seizures and increased number of seizures). Results: The study enrolled 259 patients (141 female and 118 male), with mean age 7 years (3,0-12.0). Comorbidities were present at 129/259 (49.8%) patients. After 12 months of treatment, 25/259 (9.7%) patients had seizure reduction >50%, 30/259 (11.6%) patients had seizure reduction <50%, 154/259 (56.5%) patients had achieved seizure freedom, 31/259 (12%) patients had same number of seizures, while 19/259 (7.3%) patients had increased number of seizures. Seizure frequency between responders and non-responders, before treatment and after 12 months of treatment was statistically significant (p<0.001). Discussion: Non responders had the best outcome with ditherapy (30/79; 38%), while responders had the best outcome with monotherapy (161/180;89.4%). Conclusion: Levetiracetam is efficient antiepileptic drug for different types of epilepsies in childhood, used as mono, di or polytherapy.


Assuntos
Epilepsia , Levetiracetam , Criança , Feminino , Humanos , Masculino , Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Levetiracetam/efeitos adversos , Estudos Prospectivos , Convulsões/tratamento farmacológico , Convulsões/induzido quimicamente , Resultado do Tratamento , Pré-Escolar
2.
Open Biol ; 14(4): 230383, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38629124

RESUMO

Non-clustered protocadherins (ncPcdhs) are adhesive molecules with spatio-temporally regulated overlapping expression in the developing nervous system. Although their unique role in neurogenesis has been widely studied, their combinatorial role in brain physiology and pathology is poorly understood. Using probabilistic cell typing by in situ sequencing, we demonstrate combinatorial inter- and intra-familial expression of ncPcdhs in the developing mouse cortex and hippocampus, at single-cell resolution. We discovered the combinatorial expression of Protocadherin-19 (Pcdh19), a protein involved in PCDH19-clustering epilepsy, with Pcdh1, Pcdh9 or Cadherin 13 (Cdh13) in excitatory neurons. Using aggregation assays, we demonstrate a code-specific adhesion function of PCDH19; mosaic PCDH19 absence in PCDH19+9 and PCDH19 + CDH13, but not in PCDH19+1 codes, alters cell-cell interaction. Interestingly, we found that PCDH19 as a dominant protein in two heterophilic adhesion codes could promote trans-interaction between them. In addition, we discovered increased CDH13-mediated cell adhesion in the presence of PCDH19, suggesting a potential role of PCDH19 as an adhesion mediator of CDH13. Finally, we demonstrated novel cis-interactions between PCDH19 and PCDH1, PCDH9 and CDH13. These observations suggest that there is a unique combinatorial code with a cell- and region-specific characteristic where a single molecule defines the heterophilic cell-cell adhesion properties of each code.


Assuntos
Epilepsia , Protocaderinas , Camundongos , Animais , Adesão Celular , Encéfalo , Epilepsia/metabolismo , Neurônios/metabolismo
3.
Clin Transl Sci ; 17(4): e13793, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38618871

RESUMO

Multiple treatment options exist for children with epilepsy, including surgery, dietary therapies, neurostimulation, and antiseizure medications (ASMs). ASMs are the first line of therapy, and more than 30 ASMs have U.S. Food and Drug Administration (FDA) approval for the treatment of various epilepsy and seizure types in children. Given the extensive FDA approval of ASMs in children, it is crucial to consider how the physiological and developmental changes throughout childhood may impact drug disposition. Various sources of pharmacokinetic (PK) variability from different extrinsic and intrinsic factors such as patients' size, age, drug-drug interactions, and drug formulation could result in suboptimal dosing of ASMs. Barriers exist to conducting clinical pharmacological studies in neonates, infants, and children due to ethical and practical reasons, limiting available data to fully characterize these drugs' disposition and better elucidate sources of PK variability. Modeling and simulation offer ways to circumvent traditional and intensive clinical pharmacology methods to address gaps in epilepsy and seizure management in children. This review discusses various physiological and developmental changes that influence the PK and pharmacodynamic (PD) variability of ASMs in children, and several key ASMs will be discussed in detail. We will also review novel trial designs in younger pediatric populations, highlight the role of extrapolation of efficacy in epilepsy, and the use of physiologically based PK modeling as a tool to investigate sources of PK/PD variability in children. Finally, we will conclude with current challenges and future directions for optimizing the efficacy and safety of these drugs across the pediatric age spectrum.


Assuntos
Epilepsia , Farmacologia Clínica , Estados Unidos , Lactente , Recém-Nascido , Humanos , Criança , Pesquisa , Convulsões/tratamento farmacológico , Simulação por Computador , Epilepsia/tratamento farmacológico
4.
Sci Rep ; 14(1): 8204, 2024 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589379

RESUMO

Seizure prediction remains a challenge, with approximately 30% of patients unresponsive to conventional treatments. Addressing this issue is crucial for improving patients' quality of life, as timely intervention can mitigate the impact of seizures. In this research field, it is critical to identify the preictal interval, the transition from regular brain activity to a seizure. While previous studies have explored various Electroencephalogram (EEG) based methodologies for prediction, few have been clinically applicable. Recent studies have underlined the dynamic nature of EEG data, characterised by data changes with time, known as concept drifts, highlighting the need for automated methods to detect and adapt to these changes. In this study, we investigate the effectiveness of automatic concept drift adaptation methods in seizure prediction. Three patient-specific seizure prediction approaches with a 10-minute prediction horizon are compared: a seizure prediction algorithm incorporating a window adjustment method by optimising performance with Support Vector Machines (Backwards-Landmark Window), a seizure prediction algorithm incorporating a data-batch (seizures) selection method using a logistic regression (Seizure-batch Regression), and a seizure prediction algorithm with a dynamic integration of classifiers (Dynamic Weighted Ensemble). These methods incorporate a retraining process after each seizure and use a combination of univariate linear features and SVM classifiers. The Firing Power was used as a post-processing technique to generate alarms before seizures. These methodologies were compared with a control approach based on the typical machine learning pipeline, considering a group of 37 patients with Temporal Lobe Epilepsy from the EPILEPSIAE database. The best-performing approach (Backwards-Landmark Window) achieved results of 0.75 ± 0.33 for sensitivity and 1.03 ± 1.00 for false positive rate per hour. This new strategy performed above chance for 89% of patients with the surrogate predictor, whereas the control approach only validated 46%.


Assuntos
Epilepsia , Qualidade de Vida , Humanos , Convulsões/diagnóstico , Epilepsia/diagnóstico , Eletroencefalografia/métodos , Algoritmos , Aprendizado de Máquina , Máquina de Vetores de Suporte
5.
Ital J Pediatr ; 50(1): 66, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594715

RESUMO

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) appears in neurological conditions where some brain areas are likely to be injured, such as deep grey matter, basal ganglia area, and white matter subcortical periventricular áreas. Moreover, modeling these brain areas in a newborn is challenging due to significant variability in the intensities associated with HIE conditions. This paper aims to evaluate functional measurements and 3D machine learning models of a given HIE case by correlating the affected brain areas with the pathophysiology and clinical neurodevelopmental. CASE PRESENTATION: A comprehensive analysis of a term infant with perinatal asphyxia using longitudinal 3D brain information from Machine Learning Models is presented. The clinical analysis revealed the perinatal asphyxia diagnosis with APGAR <5 at 5 and 10 minutes, umbilical arterial pH of 7.0 BE of -21.2 mmol / L), neonatal seizures, and invasive ventilation mechanics. Therapeutic interventions: physical, occupational, and language neurodevelopmental therapies. Epilepsy treatment: vagus nerve stimulation, levetiracetam, and phenobarbital. Furthermore, the 3D analysis showed how the volume decreases due to age, exhibiting an increasing asymmetry between hemispheres. The results of the basal ganglia area showed that thalamus asymmetry, caudate, and putamen increase over time while globus pallidus decreases. CLINICAL OUTCOMES: spastic cerebral palsy, microcephaly, treatment-refractory epilepsy. CONCLUSIONS: Slight changes in the basal ganglia and cerebellum require 3D volumetry for detection, as standard MRI examinations cannot fully reveal their complex shape variations. Quantifying these subtle neurodevelopmental changes helps in understanding their clinical implications. Besides, neurophysiological evaluations can boost neuroplasticity in children with neurological sequelae by stimulating new neuronal connections.


Assuntos
Asfixia Neonatal , Epilepsia , Hipóxia-Isquemia Encefálica , Recém-Nascido , Lactente , Gravidez , Feminino , Criança , Humanos , Asfixia/complicações , Encéfalo/diagnóstico por imagem , Hipóxia-Isquemia Encefálica/diagnóstico por imagem , Hipóxia-Isquemia Encefálica/terapia , Hipóxia-Isquemia Encefálica/complicações , Asfixia Neonatal/complicações , Asfixia Neonatal/diagnóstico por imagem , Asfixia Neonatal/terapia , Convulsões/complicações
6.
Cell Biochem Funct ; 42(3): e4003, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38597235

RESUMO

Neuronal pentraxin 2 (Nptx2), a member of the synaptic protein family linked to excitatory synaptic formation, is found to be upregulated in epileptic mice, yet its role in epilepsy has been unclear. In vivo, we constructed a mouse model of epilepsy by using kainic acid induction. In vitro experiments, a Mg2+-free medium was used to induce epileptiform discharges in neurons. The results showed that the Nptx2 was upregulated in epileptic mice. Moreover, Nptx2 knockdown reduced the number of seizures and seizure duration. Knocking down Nptx2 not only reduced the number and duration of seizures but also showed a decrease in electroencephalogram amplitude. Behavioral tests indicated improvements in learning and memory abilities after Nptx2 knockdown. The Nissl staining and Timms staining revealed that Nptx2 silencing mitigated epilepsy-induced brain damage. The immunofluorescence staining revealed that Nptx2 absence resulted in a reduction of apoptosis. Nptx2 knockdown reduced Bax, cleaved caspase3, and cleaved caspase9 expression, while increased Bcl-2 expression. Notably, Nptx2 knockdown inhibited GluA1 phosphorylation at the S831 site and reduced the GluA1 membrane expression. The PSD95 expression declined in the epilepsy model, while the Nptx2 knockdown reversed it. Collectively, our study indicated that Nptx2 silencing not only alleviated brain damage and neuron apoptosis but also improved learning and memory ability in epileptic mice, suggesting Nptx2 as a promising target for epilepsy treatment.


Assuntos
Epilepsia , Proteínas do Tecido Nervoso , Convulsões , Camundongos , Animais , Fosforilação , Convulsões/induzido quimicamente , Convulsões/metabolismo , Epilepsia/induzido quimicamente , Epilepsia/metabolismo , Proteína C-Reativa/genética , Proteína C-Reativa/efeitos adversos , Proteína C-Reativa/metabolismo , Hipocampo/metabolismo
7.
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
8.
Acta Neurobiol Exp (Wars) ; 84(1): 35-42, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38587326

RESUMO

Alarin is a newly discovered neuropeptide that belongs to the galanin peptide family with a wide range of bioactivity in the nervous system. Its function in the brain's autonomic areas has been studied, and it has been reported that alarin is involved in the regulation of excitability in hypothalamic neurons. Its role in the regulation of excitability in the hippocampus, however, is unknown. In this study, we investigated if alarin induced any synchronous discharges or epileptiform activity, and if it had any effect on already initiated epileptiform discharges. We used thick acute horizontal hippocampal slices obtained from 30­ to 35­day­old rats. Extracellular field potential recordings were evaluated in the CA1 region of the hippocampus. Our data demonstrated that, alarin application did not result in any epileptiform activity or abnormal discharges. 4­aminopyridine was applied to induce epileptiform activity in the slices. We found that alarin increased the frequency of interictal­like events and the mean power of local field potentials in the CA1 region of the hippocampus, which was induced by 4­aminopyridine. These results demonstrated for the first time that alarin has a modulatory effect on synchronized neuronal discharges and showed the contribution of the neuropeptide alarin to epilepsy­like conditions.


Assuntos
Epilepsia , Peptídeo Semelhante a Galanina , Ratos , Animais , Hipocampo , Epilepsia/induzido quimicamente , Peptídeo Semelhante a Galanina/farmacologia , 4-Aminopiridina/farmacologia
9.
Acta Neurobiol Exp (Wars) ; 84(1): 51-58, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38587324

RESUMO

Levetiracetam (LEV) is a drug commonly used as an anticonvulsant. However, recent evidence points to a possible role as an antioxidant. We previously demonstrated the antioxidant properties of LEV by significantly increasing catalase and superoxide dismutase activities and decreasing the hydrogen peroxide (H2O2) levels in the hippocampus of rats with temporal lobe epilepsy (TLE) showing scavenging properties against the hydroxyl radical. The aim of the present work was to evaluate, the effect of LEV on DNA oxidation, by determining 8­hydroxy­2­deoxyguanosine (8­OHdG) levels, and glutathione content, through reduced (GSH) and oxidized (GSSG) glutathione levels, in the hippocampus of rats with TLE. Male Wistar rats were assigned to the control (CTRL), CTRL+LEV, epileptic (EPI) and EPI+LEV groups. TLE was induced using the lithium­pilocarpine model. Thirteen weeks after TLE induction, LEV was administered for one week through osmotic pumps implanted subcutaneously. The determination of 8­OHdG, GSH and GSSG levels were measured using spectrophotometric methods. We showed that LEV alone significantly increased 8­OHdG and GSSG levels in the hippocampus of control rats compared to those in epileptic condition. No significant differences in GSH levels were observed. LEV could induce changes in the hippocampus increasing DNA oxidation and GSSG levels under nonepileptic condition but not protecting against the mitochondrial dysfunction observed in TLE probably by mechanisms related to changes in chromatin structure, neuroinflammation and alterations in redox components.


Assuntos
Epilepsia do Lobo Temporal , Epilepsia , Piracetam , Masculino , Ratos , Animais , Levetiracetam/efeitos adversos , Epilepsia do Lobo Temporal/induzido quimicamente , Epilepsia do Lobo Temporal/tratamento farmacológico , Piracetam/efeitos adversos , Antioxidantes/uso terapêutico , Dissulfeto de Glutationa/efeitos adversos , Peróxido de Hidrogênio/efeitos adversos , Ratos Wistar , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Glutationa/metabolismo , Oxirredução
10.
Sci Rep ; 14(1): 7952, 2024 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575623

RESUMO

To investigate the effectiveness of AcceleDent Aura vibrating device on the rate of canine retraction. Thirty-two patients requiring extraction of upper first premolars and canine retraction were randomly allocated with a 1:1 ratio into either no-appliance group or the AcceleDent Aura appliance group. Canine retraction was done applying 150gm of retraction force using NiTi coil springs on 16 × 22 stainless steel archwires. The duration of the study was 4 months. Models were collected and digitized directly after extraction of upper first premolars and at monthly intervals during canine retraction for recording the monthly as well as the total distance moved by the canine. Digitized models were superimposed on the initial model and data were statistically analyzed. Anchorage loss, rotation, tipping, torque and root condition were evaluated using cone beam computed tomography imaging. Pain was evaluated by visual analog scale. No patients were dropped-out during this study. There was no statistically significant difference between both groups regarding the total distance travelled by the canine (P = 0.436), as well as the rate of canine retraction per month (P = 0.17). Root condition was the same for the two groups. Regarding the pain level, there was no statistically significant difference between the two groups at day 0 (P = 0.721), after 24 h (P = 0.882), after 72 h (P = 0.378) and after 7 days (P = 0.964). AcceleDent Aura was not able to accelerate orthodontic tooth movement. Pain level couldn't be reduced by vibrational force with an AcceleDent device during orthodontic treatment. Root condition was not affected by the vibrational forces.


Assuntos
Epilepsia , Vibração , Humanos , Vibração/uso terapêutico , Dente Canino/diagnóstico por imagem , Técnicas de Movimentação Dentária/métodos , Dor
11.
Sci Adv ; 10(14): eadl2764, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579001

RESUMO

Despite seizure control by early high-dose pyridoxine (vitamin B6) treatment, at least 75% of pyridoxine-dependent epilepsy (PDE) patients with ALDH7A1 mutation still suffer from intellectual disability. It points to a need for additional therapeutic interventions for PDE beyond pyridoxine treatment, which provokes us to investigate the mechanisms underlying the impairment of brain hemostasis by ALDH7A1 deficiency. In this study, we show that ALDH7A1-deficient mice with seizure control exhibit altered adult hippocampal neurogenesis and impaired cognitive functions. Mechanistically, ALDH7A1 deficiency leads to the accumulation of toxic lysine catabolism intermediates, α-aminoadipic-δ-semialdehyde and its cyclic form, δ-1-piperideine-6-carboxylate, which in turn impair de novo pyrimidine biosynthesis and inhibit NSC proliferation and differentiation. Notably, supplementation of pyrimidines rescues abnormal neurogenesis and cognitive impairment in ALDH7A1-deficient adult mice. Therefore, our findings not only define the important role of ALDH7A1 in the regulation of adult hippocampal neurogenesis but also provide a potential therapeutic intervention to ameliorate the defective mental capacities in PDE patients with seizure control.


Assuntos
Ácido 2-Aminoadípico/análogos & derivados , Aldeído Desidrogenase , Epilepsia , Piridoxina , Humanos , Animais , Camundongos , Piridoxina/farmacologia , Convulsões/tratamento farmacológico , Convulsões/etiologia , Pirimidinas/farmacologia , Cognição
12.
J Mol Neurosci ; 74(2): 39, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581598

RESUMO

Previous studies have indicated a potential relationship between zinc and epilepsy. The aim of this study is to investigate the causal relationship between zinc, zinc-dependent carbonic anhydrase, and gray matter volume in brain regions enriched with zinc and epilepsy, as well as explore the possible mechanisms by which zinc contributes to epilepsy. First, this study assessed the risk causality between zinc, carbonic anhydrase, and gray matter volume alterations in zinc-enriched brain regions and various subtypes of epilepsy based on Two-sample Mendelian randomization analysis. And then, this study conducted GO/KEGG analysis based on colocalization analysis, MAGMA analysis, lasso regression, random forest model, and XGBoost model. The results of Mendelian randomization analyses showed a causal relationship between zinc, carbonic anhydrase-4, and generalized epilepsy (p = 0.044 , p = 0.010). Additionally, carbonic anhydrase-1 and gray matter volume of the caudate nucleus were found to be associated with epilepsy and focal epilepsy (p = 0.014, p = 0.003 and p = 0.022, p = 0.009). A colocalization relationship was found between epilepsy and focal epilepsy (PP.H4.abf = 97.7e - 2). Meanwhile, the MAGMA analysis indicated that SNPs associated with epilepsy and focal epilepsy were functionally localized to zinc-finger-protein-related genes (p < 1.0e - 5). The genes associated with focal epilepsy were found to have a molecular function of zinc ion binding (FDR = 2.3e - 6). After the onset of epilepsy, the function of the gene whose expression changed in the rats with focal epilepsy was enriched in the biological process of vascular response (FDR = 4.0e - 5). These results revealed mechanism of the increased risk of epilepsy caused by elevated zinc may be related to the increase of zinc ion-dependent carbonic anhydrase or the increase of the volume of zinc-rich caudate gray matter.


Assuntos
Anidrases Carbônicas , Epilepsias Parciais , Epilepsia , Ratos , Animais , Zinco/metabolismo , Anidrases Carbônicas/genética , Anidrases Carbônicas/análise , Anidrases Carbônicas/metabolismo , Encéfalo/metabolismo , Epilepsia/genética
13.
Int J Mol Sci ; 25(7)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38612542

RESUMO

The intricate relationship between viruses and epilepsy involves a bidirectional interaction. Certain viruses can induce epilepsy by infecting the brain, leading to inflammation, damage, or abnormal electrical activity. Conversely, epilepsy patients may be more susceptible to viral infections due to factors, such as compromised immune systems, anticonvulsant drugs, or surgical interventions. Neuroinflammation, a common factor in both scenarios, exhibits onset, duration, intensity, and consequence variations. It can modulate epileptogenesis, increase seizure susceptibility, and impact anticonvulsant drug pharmacokinetics, immune system function, and brain physiology. Viral infections significantly impact the clinical management of epilepsy patients, necessitating a multidisciplinary approach encompassing diagnosis, prevention, and treatment of both conditions. We delved into the dual dynamics of viruses inducing epilepsy and epilepsy patients acquiring viruses, examining the unique features of each case. For virus-induced epilepsy, we specify virus types, elucidate mechanisms of epilepsy induction, emphasize neuroinflammation's impact, and analyze its effects on anticonvulsant drug pharmacokinetics. Conversely, in epilepsy patients acquiring viruses, we detail the acquired virus, its interaction with existing epilepsy, neuroinflammation effects, and changes in anticonvulsant drug pharmacokinetics. Understanding this interplay advances precision therapies for epilepsy during viral infections, providing mechanistic insights, identifying biomarkers and therapeutic targets, and supporting optimized dosing regimens. However, further studies are crucial to validate tools, discover new biomarkers and therapeutic targets, and evaluate targeted therapy safety and efficacy in diverse epilepsy and viral infection scenarios.


Assuntos
Epilepsia , Viroses , Vírus , Humanos , Anticonvulsivantes/uso terapêutico , Doenças Neuroinflamatórias , Viroses/complicações , Viroses/tratamento farmacológico , Epilepsia/tratamento farmacológico , Epilepsia/etiologia , Biomarcadores
14.
Int J Mol Sci ; 25(7)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38612920

RESUMO

X-linked epilepsies are a heterogeneous group of epileptic conditions, which often overlap with X-linked intellectual disability. To date, various X-linked genes responsible for epilepsy syndromes and/or developmental and epileptic encephalopathies have been recognized. The electro-clinical phenotype is well described for some genes in which epilepsy represents the core symptom, while less phenotypic details have been reported for other recently identified genes. In this review, we comprehensively describe the main features of both X-linked epileptic syndromes thoroughly characterized to date (PCDH19-related DEE, CDKL5-related DEE, MECP2-related disorders), forms of epilepsy related to X-linked neuronal migration disorders (e.g., ARX, DCX, FLNA) and DEEs associated with recently recognized genes (e.g., SLC9A6, SLC35A2, SYN1, ARHGEF9, ATP6AP2, IQSEC2, NEXMIF, PIGA, ALG13, FGF13, GRIA3, SMC1A). It is often difficult to suspect an X-linked mode of transmission in an epilepsy syndrome. Indeed, different models of X-linked inheritance and modifying factors, including epigenetic regulation and X-chromosome inactivation in females, may further complicate genotype-phenotype correlations. The purpose of this work is to provide an extensive and updated narrative review of X-linked epilepsies. This review could support clinicians in the genetic diagnosis and treatment of patients with epilepsy featuring X-linked inheritance.


Assuntos
Epilepsia , Espasmos Infantis , Feminino , Humanos , Genes Ligados ao Cromossomo X , Epigênese Genética , Genes cdc , Epilepsia/genética , Receptor de Pró-Renina , Protocaderinas , Fatores de Troca do Nucleotídeo Guanina , Fatores de Troca de Nucleotídeo Guanina Rho , N-Acetilglucosaminiltransferases
15.
Cereb Cortex ; 34(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38615241

RESUMO

Focal cortical dysplasias are abnormalities of the cerebral cortex associated with an elevated risk of neurological disturbances. Cortical spreading depolarization/depression is a correlate of migraine aura/headache and a trigger of migraine pain mechanisms. However, cortical spreading depolarization/depression is associated with cortical structural changes, which can be classified as transient focal cortical dysplasias. Migraine is reported to be associated with changes in various brain structures, including malformations and lesions in the cortex. Such malformations may be related to focal cortical dysplasias, which may play a role in migraine pathogenesis. Results obtained so far suggest that focal cortical dysplasias may belong to the causes and consequences of migraine. Certain focal cortical dysplasias may lower the threshold of cortical excitability and facilitate the action of migraine triggers. Migraine prevalence in epileptic patients is higher than in the general population, and focal cortical dysplasias are an established element of epilepsy pathogenesis. In this narrative/hypothesis review, we present mainly information on cortical structural changes in migraine, but studies on structural alterations in deep white matter and other brain regions are also presented. We develop the hypothesis that focal cortical dysplasias may be causally associated with migraine and link pathogeneses of migraine and epilepsy.


Assuntos
Epilepsia , Displasia Cortical Focal , Transtornos de Enxaqueca , Humanos , Transtornos de Enxaqueca/etiologia , Encéfalo , Córtex Cerebral , Epilepsia/etiologia
16.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(3): 515-522, 2024 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-38597443

RESUMO

OBJECTIVE: To explore the inhibitory effect of saikosonin a (SSa) on pentylenetetrazol-induced acute epilepsy seizures in a mouse model of depression and explore the mechanism mediating this effect. METHODS: Male C57BL/6J mouse models of depression was established by oral administration of corticosterone via drinking water for 3 weeks, and acute epileptic seizures were induced by intraperitoneal injection of a single dose of pentylenetetrazole. The effect of intraperitoneal injection of SSa prior to the treatment on depressive symptoms and epileptic seizures were assessed using behavioral tests, epileptic seizure grading and hippocampal morphology observation. ELISA was used to detect blood corticosterone levels of the mice, and RTqPCR was performed to detect the pro- and anti-inflammatory factors. Microglia activation in the mice was observed using immunofluorescence staining. RESULTS: The mouse model of corticosterone-induced depression showed body weight loss and obvious depressive behaviors with significantly increased serum corticosterone level (all P < 0.05). Compared with those with pentylenetetrazole-induced epilepsy alone, the epileptic mice with comorbid depression showed significantly shorter latency of epileptic seizures, increased number, grade and duration of of seizures, reduced Nissl bodies in hippocampal CA1 and CA3 neurons, increased number of Iba1-positive cells, and significantly enhanced hippocampal expressions of IL-1ß, IL-10, TNF-α and IFN-γ. Pretreatment of the epileptic mice with SSa significantly prolonged the latency of epileptic seizures, reduced the number, duration, and severity of seizures, increased the number of Nissl bodies, decreased the number of Iba1-positive cells, and reduced the expression levels of IL-1ß, IL-10, TNF-α, and IFN-γ in the hippocampus (P < 0.05). CONCLUSION: Depressive state aggravates epileptic seizures, increases microglia activation, and elevates inflammation levels. SSA treatment can alleviate acute epileptic seizures in mouse models of depression possibly by suppressing microglia activation-mediated inflammation.


Assuntos
Epilepsia , Ácido Oleanólico/análogos & derivados , Pentilenotetrazol , Saponinas , Masculino , Camundongos , Animais , Pentilenotetrazol/efeitos adversos , Interleucina-10 , Microglia/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Depressão , Corticosterona/metabolismo , Corticosterona/farmacologia , Corticosterona/uso terapêutico , Camundongos Endogâmicos C57BL , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/metabolismo , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Epilepsia/metabolismo , Hipocampo/metabolismo , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Modelos Animais de Doenças
17.
Rev Neurol ; 78(8): 237, 2024 Apr 16.
Artigo em Espanhol | MEDLINE | ID: mdl-38618671

RESUMO

TITLE: Relevancia de la adhesión al tratamiento en el control de la epilepsia.


Assuntos
Epilepsia , Humanos , Epilepsia/tratamento farmacológico
18.
Nat Commun ; 15(1): 3156, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605017

RESUMO

Modulating brain oscillations has strong therapeutic potential. Interventions that both non-invasively modulate deep brain structures and are practical for chronic daily home use are desirable for a variety of therapeutic applications. Repetitive audio-visual stimulation, or sensory flicker, is an accessible approach that modulates hippocampus in mice, but its effects in humans are poorly defined. We therefore quantified the neurophysiological effects of flicker with high spatiotemporal resolution in patients with focal epilepsy who underwent intracranial seizure monitoring. In this interventional trial (NCT04188834) with a cross-over design, subjects underwent different frequencies of flicker stimulation in the same recording session with the effect of sensory flicker exposure on local field potential (LFP) power and interictal epileptiform discharges (IEDs) as primary and secondary outcomes, respectively. Flicker focally modulated local field potentials in expected canonical sensory cortices but also in the medial temporal lobe and prefrontal cortex, likely via resonance of stimulated long-range circuits. Moreover, flicker decreased interictal epileptiform discharges, a pathological biomarker of epilepsy and degenerative diseases, most strongly in regions where potentials were flicker-modulated, especially the visual cortex and medial temporal lobe. This trial met the scientific goal and is now closed. Our findings reveal how multi-sensory stimulation may modulate cortical structures to mitigate pathological activity in humans.


Assuntos
Epilepsias Parciais , Epilepsia , Humanos , Camundongos , Animais , Eletroencefalografia , Encéfalo , Lobo Temporal
19.
Transl Psychiatry ; 14(1): 186, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605027

RESUMO

Deep brain stimulation (DBS) modulates local and widespread connectivity in dysfunctional networks. Positive results are observed in several patient populations; however, the precise mechanisms underlying treatment remain unknown. Translational DBS studies aim to answer these questions and provide knowledge for advancing the field. Here, we systematically review the literature on DBS studies involving models of neurological, developmental and neuropsychiatric disorders to provide a synthesis of the current scientific landscape surrounding this topic. A systematic analysis of the literature was performed following PRISMA guidelines. 407 original articles were included. Data extraction focused on study characteristics, including stimulation protocol, behavioural outcomes, and mechanisms of action. The number of articles published increased over the years, including 16 rat models and 13 mouse models of transgenic or healthy animals exposed to external factors to induce symptoms. Most studies targeted telencephalic structures with varying stimulation settings. Positive behavioural outcomes were reported in 85.8% of the included studies. In models of psychiatric and neurodevelopmental disorders, DBS-induced effects were associated with changes in monoamines and neuronal activity along the mesocorticolimbic circuit. For movement disorders, DBS improves symptoms via modulation of the striatal dopaminergic system. In dementia and epilepsy models, changes to cellular and molecular aspects of the hippocampus were shown to underlie symptom improvement. Despite limitations in translating findings from preclinical to clinical settings, rodent studies have contributed substantially to our current knowledge of the pathophysiology of disease and DBS mechanisms. Direct inhibition/excitation of neural activity, whereby DBS modulates pathological oscillatory activity within brain networks, is among the major theories of its mechanism. However, there remain fundamental questions on mechanisms, optimal targets and parameters that need to be better understood to improve this therapy and provide more individualized treatment according to the patient's predominant symptoms.


Assuntos
Estimulação Encefálica Profunda , Epilepsia , Camundongos , Humanos , Ratos , Animais , Estimulação Encefálica Profunda/métodos , Roedores , Encéfalo , Hipocampo
20.
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
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