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2.
Epileptic Disord ; 25(5): 749-757, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37589547

RESUMO

OBJECTIVE: Rasmussen Encephalitis (RE) is a rare inflammatory neurodegenerative disease associated with refractory seizures, hemiparesis, and cognitive deterioration, due to lateralized cortical atrophy. Hemispheric surgery (hemispherotomy) is the mainstay of treatment, but its unavoidable motor deficits and lack of long-term data regarding seizure outcomes can make patients and families apprehensive to undergo this procedure. The present study aimed at analyzing the results of surgical treatment for RE from a motor and epilepsy standpoint, and mitigate such concerns. METHODS: Clinical and operative data were retrospectively collected from medical records of pharmacoresistant patients treated with functional hemispherectomy at a tertiary reference center for epilepsy surgery, during a 24-year period (1996-2020). Variables such as age of epilepsy onset, seizure semiology, seizure frequency, immunomodulatory therapy, age at surgery, duration of epilepsy, surgical procedures and complications, number of medications used preoperatively and postoperatively were described and statistically analyzed. RESULTS: Forty-three (43) patients were included in this study. Mean age of epilepsy onset was 6.14 years, the average interval between epilepsy onset and hemispherotomy was 2.21 years. and the mean age at surgery was 8.28 years. Thirty patients (69.7%) were Engel I at their last follow-up, of whom 23 (56.4%) were Engel Ia, within a mean follow-up of 11.3 years. Duration of epilepsy, seizure frequency, and age at surgery, among others, did not correlate with seizure outcome, except the use of immunotherapy which led to worse outcomes (p < .05). Also, after surgery, motor functionality was significantly recovered (i.e., most patients returned to their previous status) with time. SIGNIFICANCE: This study tackled some issues regarding the surgical treatment of this disease, particularly showing that hemispherotomy is safe and leads to potentially recoverable disability of motor functions while providing high rates of effective and long-lasting seizure control; therefore, early surgical indication should be warranted once medical refractoriness has been established.


Assuntos
Encefalite , Epilepsia , Hemisferectomia , Doenças Neurodegenerativas , Criança , Humanos , Resultado do Tratamento , Estudos Retrospectivos , Doenças Neurodegenerativas/complicações , Convulsões/cirurgia , Convulsões/complicações , Hemisferectomia/efeitos adversos , Encefalite/complicações
3.
Childs Nerv Syst ; 39(5): 1193-1200, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36580119

RESUMO

PURPOSE: We aimed to analyze the potential for postoperative (PO) medication suspension and reduction, emphasizing passive withdrawal. METHODS: Retrospective study of patients under 18 years old submitted to surgical treatment for pharmacoresistant epilepsy and classified as Engel I during the first year of PO follow-up. Therapeutic management was evaluated through discontinuation or reduction of medications, both in terms of the number of ASM prescribed and in daily maintenance dosages in mg/kg. RESULTS: ASM withdrawal started in the first year PO and occurred in 1.2% of cases, with a significant yearly reduction in the number of ASM during follow-up (p < 0.001). A comparison of the most commonly used ASM in daily mg/kg between the preoperative period (preop) and PO showed a reduction of ASM maintenance dosages during PO. Even though recurrence of seizures was observed 5 years after surgery, 125 patients (85%) were still classified as Engel I, albeit a higher number of ASM per patient was observed. Most patients showed no changes in cognitive and adaptive behavior evaluation between preop and PO, even in those who were able to reduce ASM. CONCLUSION: Significant reduction observed both in the number and daily maintenance dosages of ASM following each year of PO may be an indirect measure of the effectiveness of epilepsy surgery.


Assuntos
Anticonvulsivantes , Epilepsia , Humanos , Criança , Adolescente , Estudos Retrospectivos , Anticonvulsivantes/uso terapêutico , Anticonvulsivantes/efeitos adversos , Resultado do Tratamento , Epilepsia/tratamento farmacológico , Epilepsia/cirurgia , Procedimentos Neurocirúrgicos
4.
Mol Med Rep ; 21(4): 1685-1701, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32319641

RESUMO

Epilepsy is a common, serious neurological disorder worldwide. Although this disease can be successfully treated in most cases, not all patients respond favorably to medical treatments, which can lead to pharmacoresistant epilepsy. Drug­resistant epilepsy can be caused by a number of mechanisms that may involve environmental and genetic factors, as well as disease­ and drug­related factors. In recent years, numerous studies have demonstrated that genetic variation is involved in the drug resistance of epilepsy, especially genetic variations found in drug resistance­related genes, including the voltage­dependent sodium and potassium channels genes, and the metabolizer of endogenous and xenobiotic substances genes. The present review aimed to highlight the genetic variants that are involved in the regulation of drug resistance in epilepsy; a comprehensive understanding of the role of genetic variation in drug resistance will help us develop improved strategies to regulate drug resistance efficiently and determine the pathophysiological processes that underlie this common human neurological disease.


Assuntos
Resistência a Medicamentos/genética , Epilepsia/tratamento farmacológico , Epilepsia/genética , Variação Genética , Epilepsia/diagnóstico , Humanos
5.
Epilepsy Behav ; 103(Pt A): 106498, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31653605

RESUMO

BACKGROUND: Nonadherence rates among people with epilepsy (PWE) are widely variable, ranging from 26% to 95.4%. We aimed to identify nonadherence in Brazil, its determinant factors, its impact on patients' management, and to compare it with other chronic nonparoxysmal diseases. METHODS: A multicenter observational case-control study was conducted between March 2015 and October 2016, and 153 subjects were included. Subjects' clinical-epidemiological data were surveyed with the Morisky-Green test (MGT), Brief Medication Questionnaire (BMQ), and the Liverpool adverse events profile (LAEP). RESULTS: One hundred three PWE and 50 controls with other, nonparoxysmal chronic conditions were interviewed; both groups were matched according to age and socioeducational level. People with epilepsy were aged 36.4 ±â€¯13.9 (range 18-67), 55% were women, mean age at epilepsy onset was 18.1 ±â€¯15.5 years, 51.5% had pharmacoresistant epilepsy, and 48.5% were on monotherapy. 74.8% of patients and 70.0% controls were nonadherent to treatment according to MGT (p = 0.58); and barrier of recall (BMQ) was associated with nonadherence in 78% of PWE and 76% of controls (p = 0.84). Binary logistic regression analysis revealed LAEP (OR 1.05; 95%CI = 1.01-1.09; p = 0.03) and self-reported frequency of forgetfulness on the last three months (OR 19.13; 95%CI = 2.40-152.28; p < 0.01) as the main factors associated with nonadherence. Nonadherent subjects did not have more seizures and did not need emergency treatment more often than adherent ones. CONCLUSION: Three of four PWE were not fully adherent to their treatment. Adherence assessment should be routine in all outpatient visits as well as interventions aimed to improving it. Adverse events are important predictors of adherence, and they should be considered when choosing the initial treatment of epilepsy.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Epilepsia/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato , Adulto Jovem
6.
Front Neurol ; 9: 65, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29479337

RESUMO

Transcranial direct current stimulation (tDCS) is a reemerged noninvasive cerebral therapy used to treat patients with epilepsy, including focal cortical dysplasia, with controversial results. We present a case of a 28-year-old female with left frontal cortical dysplasia refractory to antiepileptic drugs, characterized by 10-15 daily right tonic hemi-body seizures. The patient received a total of seven sessions of cathodal tDCS (2 mA, 30 min). The first three sessions were applied over three consecutive days, and the remaining four sessions of tDCS were given each at 2-week intervals. At the 1-year follow-up, the patient reported to have a single seizure per month and only mild adverse events.

7.
Mol Neurobiol ; 55(5): 3698-3708, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28527108

RESUMO

A body of evidence supports a relevant role of brain-derived neurotrophic factor (BDNF) in temporal lobe epilepsy (TLE). Magnetic resonance data reveal that the cerebral atrophy extends to regions that are functionally and anatomically connected with the hippocampus, especially the temporal cortex. We previously reported an increased expression of BDNF messenger for the exon VI in the hippocampus of temporal lobe epilepsy patients compared to an autopsy control group. Altered levels of this particular transcript were also associated with pre-surgical use of certain psychotropic. We extended here our analysis of transcripts I, II, IV, and VI to the temporal cortex since this cerebral region holds intrinsic communication with the hippocampus and is structurally affected in patients with TLE. We also assayed the cyclic adenosine monophosphate response element-binding (CREB) and glucocorticoid receptor (GR) genes as there is experimental evidence of changes in their expression associated with BDNF and epilepsy. TLE and pre-surgical pharmacological treatment were considered as the primary clinical independent variables. Transcripts BDNF I and BDNF VI increased in the temporal cortex of patients with pharmacoresistant TLE. The expression of CREB and GR expression follow the same direction. Pre-surgical use of selective serotonin reuptake inhibitors, carbamazepine (CBZ) and valproate (VPA), was associated with the differential expression of specific BDNF transcripts and CREB and GR genes. These changes could have functional implication in the plasticity mechanisms related to temporal lobe epilepsy.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Córtex Cerebral/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Epilepsia do Lobo Temporal/metabolismo , Receptores de Glucocorticoides/metabolismo , Adolescente , Idoso , Fator Neurotrófico Derivado do Encéfalo/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Epilepsia do Lobo Temporal/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Glucocorticoides/genética , Adulto Jovem
8.
Neuroscience ; 314: 12-21, 2016 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-26621122

RESUMO

A putative role of the brain-derived neurotrophic factor (BDNF) in epilepsy has emerged from in vitro and animal models, but few studies have analyzed human samples. We assessed the BDNF expression of transcripts with exons I (BDNFI), II (BDNFII), IV (BDNFIV) and VI (BDNFVI) and methylation levels of promoters 4 and 6 in the hippocampi of patients with pharmaco-resistant temporal lobe epilepsy (TLE) (n=24). Hippocampal sclerosis (HS) and pre-surgical pharmacological treatment were considered as clinical independent variables. A statistical significant increase for the BDNFVI (p<0.05) was observed in TLE patients compared to the autopsy control group (n=8). BDNFVI was also increased in anxiety/depression TLE (N=4) when compared to autopsies or to the remaining group of patients (p<0.05). In contrast, the use of the antiepileptic drug Topiramate (TPM) (N=3) was associated to a decrease in BDNFVI expression (p<0.05) when compared to the remaining group of patients. Methylation levels at the BDNF promoters 4 and 6 were similar between TLE and autopsies and in relation to the use of either Sertraline (SRT) or TPM. These results suggest an up-regulated expression of a specific BDNF transcript in patients with TLE, an effect that seems to be dependent on the use of specific drugs.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Epilepsia do Lobo Temporal/genética , Hipocampo/metabolismo , Adulto , Idoso , Anticonvulsivantes/uso terapêutico , Metilação de DNA , Epilepsia do Lobo Temporal/tratamento farmacológico , Éxons , Feminino , Frutose/análogos & derivados , Frutose/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Sertralina/uso terapêutico , Topiramato , Adulto Jovem
9.
Seizure ; 31: 7-11, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26362370

RESUMO

PURPOSE: Temporal lobe epilepsy (TLE) is the most common variety of focal epilepsy among adults. The neuroinflammatory mechanisms of epilepsies may be involved in the genesis of seizures and refractory epilepsies, particularly in the case of progressive syndromes such as TLE associated with mesial hippocampal sclerosis (TLE-HS). The goal of the present study is investigate the genetic profile of susceptibility of individuals with TLE-HS by analyzing the possible association of TLE-HS with human leukocyte antigen (HLA) DRB1, DQA1 and DQB1 alleles. METHODS: Peripheral blood samples were collected from 42 individuals with pharmacoresistant TLE-HS and 89 healthy controls. The typing of the HLA class II alleles from DRB1, DQB1, and DQA1 loci were analyzed using sequence-specific primer-polymerase chain reaction (SSP-PCR) and identified through sequencing. Statistical analysis of relative allele frequencies was performed using an Excel spreadsheet; p-value, relative risk (RR), and odds ratio (OR) were calculated using the software Epi Info 6.0. p-values <0.05 following Bonferroni's method correction were considered statistically significant. RESULTS: HLA-DRB1*13:02 was the only allele with a statistically significant difference (p=0.01) in frequency between patients and controls. However, the significance was lost following Bonferroni's method correction (p=0.44). The remainder of the alleles in the HLA-DRB1, HLA-DQB1 and HLA-DQA1 regions did not exhibit any significant association. CONCLUSION: The allele HLA DRB1*13:02 has exhibited a tendency to behave as a susceptibility factor for TLE-HS.


Assuntos
Epilepsia Resistente a Medicamentos/genética , Epilepsia do Lobo Temporal/genética , Predisposição Genética para Doença , Cadeias alfa de HLA-DQ/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Adolescente , Adulto , Idoso , Epilepsia Resistente a Medicamentos/patologia , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Hipocampo/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose , Adulto Jovem
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