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1.
Ann Neurol ; 87(1): 22-29, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31714640

RESUMO

OBJECTIVE: Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) is widely established for older generation AEDs, whereas there is limited evidence about newer AEDs. Our aim is to assess the benefit of TDM of newer generation AEDs in epilepsy. METHODS: We performed a randomized, controlled trial comparing systematic with rescue TDM of lamotrigine, levetiracetam, oxcarbazepine, topiramate, brivaracetam, zonisamide, or pregabalin. Participants were adults with epilepsy, in whom treatment with newer generation AEDs was initiated or needed adjustment. In the systematic TDM arm, AED plasma levels were available at each appointment, whereas in the rescue TDM arm, levels were known only if a study endpoint was reached (inefficacy or adverse events). The primary outcome was the proportion of participants followed 1 year without reaching one of the predefined endpoints. RESULTS: A total of 151 participants were enrolled; global retention in the study was similar in both arms (56% overall, 58% in the systematic, and 53% in the rescue TDM arm, p = 0.6, Cox regression). There was no difference in terms of outcome regarding treatment efficacy or tolerability. Partial adherence of clinicians to TDM (adjusting or not AED dosage based on blood levels) did not explain this lack of benefit. INTERPRETATION: This study provides class A evidence that systematic drug level monitoring of newer generation AEDs does not bring tangible benefits in the management of patients with epilepsy. Poor correlation between clinical effects and drug levels likely accounts for this finding. However, TDM is useful in several situations, such as pregnancy, as well as when there are compliance issues. ANN NEUROL 2020;87:22-29.


Assuntos
Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapêutico , Monitoramento de Medicamentos/estatística & dados numéricos , Epilepsia/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/sangue , Relação Dose-Resposta a Droga , Epilepsia/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Resultado do Tratamento , Adulto Jovem
2.
Clin Biochem ; 74: 24-30, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31672648

RESUMO

BACKGROUND: In some clinical situations (pregnancy, aging, drug resistance, toxicity), measurements of lamotrigine plasma levels may be reliable. Limited studies indicate that saliva and hair could be alternative sources for monitoring lamotrigine therapy. The drug content in hair can also be used to assess the history of drug therapy and to ascertain long-term patient compliance. The aims of this study were to 1) determine the correlations among plasma, saliva, and hair lamotrigine concentrations, 2) evaluate saliva as an alternative matrix for monitoring drug levels and 3) evaluate hair as a source of information on adherence to antiepileptic treatment and on the correlation of hair concentrations with clinical outcomes in patients with epilepsy. METHODS: Plasma, saliva, and hair lamotrigine concentrations were measured by liquid chromatography-tandem mass spectrometry in positive ionization mode. The study group (n = 85) was recruited among the epileptic patients at the Institute of Psychiatry and Neurology, Warsaw, Poland. RESULTS: Plasma concentrations were not influenced by sex, age, or the concomitant use of other antiepileptic drugs. Lamotrigine saliva and plasma concentrations were strongly correlated (r = 0.82, p < 0.001). Lamotrigine hair concentrations were correlated with the plasma concentrations (r = 0.53, p < 0.001) and daily dose in mg/kg (r = 0.23, p = 0.024). The analysis revealed no significant correlation between lamotrigine hair levels and the number of seizures in the previous 3 months (r = -0.1, p > 0.05). CONCLUSIONS: The lamotrigine saliva concentration is strongly correlated with its plasma level, and saliva can be used as an alternative matrix to plasma for monitoring. Lamotrigine can also be successfully measured in hair, and the drug levels in hair tend to be correlated with the levels in plasma. However, lamotrigine levels in hair may not correspond to clinical outcomes (i.e., seizure episodes).


Assuntos
Anticonvulsivantes/análise , Monitoramento de Medicamentos/métodos , Cabelo/química , Lamotrigina/análise , Saliva/química , Adolescente , Adulto , Idoso , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/sangue , Anticonvulsivantes/uso terapêutico , Cromatografia Líquida , Epilepsia/sangue , Epilepsia/tratamento farmacológico , Feminino , Humanos , Lamotrigina/administração & dosagem , Lamotrigina/sangue , Lamotrigina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polônia , Convulsões/sangue , Convulsões/tratamento farmacológico , Espectrometria de Massas em Tandem , Adulto Jovem
3.
West Afr J Med ; 36(3): 211-216, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31622482

RESUMO

BACKGROUND: Antiepileptic drugs are necessary for successful treatment of epilepsy. Unfortunately, epilepsy itself and some antiepileptic drugs have been documented to provoke or worsen seizure frequency by altering blood levels of some oxidants and antioxidants in persons with epilepsy. OBJECTIVE: This study investigated the effect of epilepsy and antiepileptic drugs on blood levels of some oxidants and antioxidants. METHODOLOGY: This was a cross-sectional case-control study. Blood samples were obtained from 35 antiepileptic drug-experienced persons with epilepsy; 35 antiepileptic-naive persons with epilepsy; and 35 age- and- sex matched apparently healthy controls; and analysed for malondialdehyde and antioxidants (uric acid, superoxide dismutase, glutathione peroxidase and catalase) using enzyme-linked immunosorbent assay. RESULTS: One-hundred and five (105) subjects (35 patients on antiepileptic drugs, 35 newly diagnosed, antiepileptic drug-naive and 35 healthy controls) were investigated. The median ages of antiepileptic drug-experienced, antiepileptic drug-naive and healthy participants were 30.0, 26.0 and 37.0 years respectively. Persons with epilepsy had significantly higher blood levels of malondialdehyde and uric acid and lower levels of enzymatic antioxidants than healthy controls. Also, persons with epilepsy on antiepileptic drug polytherapy had signi-ficantly higher blood levels of malondialdehyde and uric acid and lower levels of enzymatic antioxidants than antiepileptic drug-naive persons with epilepsy and persons with epilepsy on antiepileptic drug monotherapy respectively. CONCLUSION: Epilepsy and antiepileptic drug significantly altered blood levels of malondialdehyde, uric acid and enzymatic antioxidants and/or their homeostatic kinetics.


Assuntos
Anticonvulsivantes/uso terapêutico , Antioxidantes/metabolismo , Epilepsia/sangue , Epilepsia/tratamento farmacológico , Eritrócitos/metabolismo , Malondialdeído/sangue , Adulto , Antioxidantes/análise , Estudos de Casos e Controles , Estudos Transversais , Humanos
4.
Epileptic Disord ; 21(4): 366-369, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31366451

RESUMO

Recently, decanoic acid (C10), a medium-chain fatty acid, was shown to be a direct inhibitor of the AMPA receptor. Accordingly, C10 has been suggested as a potential anticonvulsant factor in the ketogenic diet (KD) or the medium-chain triglyceride KD. Here, we tested whether C10 serum levels correlate with the response to KD in five children (1.5 ± 0.6 years of age) with epilepsy. The serum levels of C10 were measured before and after KD initiation (n=2 at one month, n=3 at three months, and n=1 at six months after initiation) by gas chromatography-mass spectrometry. After three months on KD, two patients were found to be responders. The mean serum level before KD initiation was 63.2 µM. Only one patient, who was a non-responder, showed an increase (5%) in C10 serum level after a month of KD. The remaining four patients (two responders) showed a decrease in the C10 level from -5.3% to -75.5%. Our preliminary data show that KD does not lead to an increase in C10 serum levels, suggesting that increased concentration of C10 might not be directly involved in the anticonvulsant effects of classic KD.


Assuntos
Ácidos Decanoicos/sangue , Dieta Cetogênica , Epilepsia/sangue , Convulsões/sangue , Adolescente , Anticonvulsivantes/uso terapêutico , Criança , Dieta Cetogênica/métodos , Epilepsia/diagnóstico , Epilepsia/tratamento farmacológico , Feminino , Humanos , Masculino , Convulsões/diagnóstico , Convulsões/tratamento farmacológico
5.
Tohoku J Exp Med ; 248(4): 273-284, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31447473

RESUMO

Lamotrigine, a frequently used antiepileptic drug, inhibits voltage-gated sodium-channels. By suppressing the release of glutamate and aspartate, lamotrigine acts as a membrane stabilizer, and it is also effective in bipolar disorder and migraine. However, lamotrigine is known to induce tremor among 4-10% of patients. We examined the lamotrigine-induced tremor in 28 epilepsy patients (age: 38.06 ± 13.56 years; 24 females and 4 males) receiving lamotrigine monotherapy and compared the data to 30 age- and sex-matched controls (age: 33.06 ± 10.71 years; 25 females and 5 males). Tremor was visually assessed by clinical tremor rating scales. Quantitative characteristics (intensity, center frequency and frequency dispersion) which are regularly used to differentiate various tremor syndromes were measured by validated, sensitive biaxial accelerometry in resting, postural and intentional positions. Regularity of repetitive finger and hand movements and reaction time were also determined. Data were statistically analyzed. Clinical tremor rating scales detected pathological tremor in three patients (10%), while accelerometry revealed tremor in seven patients (25%). Center frequency of patients with pathological tremor was similar to controls, but the frequency dispersion was significantly lower and tremor intensity was significantly higher in both postural and intentional positions. Rhythmic movements and reaction time were normal. Our results show that objective measurements detect pathological intention tremor in 25% of epilepsy patients receiving lamotrigine monotherapy. Quantitative characteristics suggest the involvement of the cerebellum in the pathomechanism of lamotrigine-induced tremor. Determining the parameters of drug-induced tremor syndromes might help to understand the complex action of tremor generator networks.


Assuntos
Cerebelo/patologia , Epilepsia/tratamento farmacológico , Lamotrigina/efeitos adversos , Lamotrigina/uso terapêutico , Tremor/induzido quimicamente , Adulto , Estudos de Casos e Controles , Cerebelo/efeitos dos fármacos , Epilepsia/sangue , Feminino , Humanos , Lamotrigina/sangue , Modelos Logísticos , Masculino , Tremor/sangue
6.
An. pediatr. (2003. Ed. impr.) ; 91(2): 88-95, ago. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-186710

RESUMO

Introducción: El deterioro cognitivo es una consecuencia común de la epilepsia en niños. El objetivo del estudio fue evaluar el cociente de los niveles de ácidos grasos omega-6 y omega-3 y su impacto en el funcionamiento cognitivo de niños con epilepsia idiopática. Pacientes y métodos: Estudio de casos y controles en 30 niños con epilepsia idiopática y 20 niños sanos. Se midieron los niveles plasmáticos de ácido alfa-linolénico (omega-3) y de ácido linoleico (omega-6) mediante cromatografía de gases. El funcionamiento cognitivo se evaluó mediante la versión en árabe de la cuarta edición de la escala de Stanford-Binet y la onda P300 en potenciales relacionados con eventos. Todos los participantes tenían un cociente intelectual superior a 70. Resultados: Los niños con epilepsia tenían niveles más bajos de omega-3 y más altos de omega 6 y un cociente omega-6/omega-3 anormal en comparación con los niños sanos. Se observó que el nivel plasmático de omega-3 se correlacionaba positivamente y el nivel de omega-6 negativamente, ambos de manera significativa, con las puntuaciones del funcionamiento cognitivo y la latencia de la onda P300 en niños con epilepsia. Conclusión: Los niños con epilepsia tienen un cociente alterado de los niveles plasmáticos de ácidos grasos omega-6 y omega-3 que se asocia al deterioro cognitivo en este grupo


Introduction: Cognitive impairment is a common consequence of epilepsy in children. This study aimed to assess the ratio of omega-6 to omega-3 fatty acid levels and its impact on cognitive function in children with idiopathic epilepsy. Patients and methods: We performed a case-control study in 30 children with idiopathic epilepsy and 20 healthy children. We measured levels of alpha-linolenic acid (omega-3) and linoleic acid (omega-6) by means of gas-liquid chromatography. We assessed cognitive function with the Arabic version of the fourth edition of the Stanford-Binet test and the P300 component of event-related potentials. All children had an intelligent quotient greater than 70. Results: Children with epilepsy had lower levels of omega-3 and higher levels of omega-6 fatty acids and an abnormal omega-6/omega-3 ratio compared to non-epileptic children. We found a significant positive correlation of serum omega-3 levels and a significant negative correlation of serum omega-6 levels with cognitive function scores and P300 latency in children with epilepsy. Conclusion: Children with epilepsy have abnormal ratios of omega-6 to omega-3 fatty acid serum levels, which is associated with impaired cognitive function in these children


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Disfunção Cognitiva/etiologia , Epilepsia/complicações , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Estudos de Casos e Controles , Cognição/fisiologia , Disfunção Cognitiva/sangue , Epilepsia/sangue
7.
An. pediatr. (2003. Ed. impr.) ; 91(2): 105-111, ago. 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-186712

RESUMO

Introducción: Los corticosteroides prenatales disminuyen la morbimortalidad neonatal, sin embargo, existen pocos estudios en países en vías de desarrollo, con resultados no consistentes. El objetivo fue cuantificar la frecuencia del uso de corticosteroides prenatales y estimar su efecto en la morbimortalidad de recién nacidos prematuros. Métodos: Estudio de cohorte retrospectivo; se seleccionaron los recién nacidos prematuros de un censo realizado entre enero de 2016 y agosto de 2017. De los expedientes maternos se registró el uso de corticosteroides; y de los expedientes de los neonatos se indagó las variables dependientes. La asociación se analizó con regresión logística, ajustada a la edad gestacional y el peso. Resultados: Se estudiaron 1.083 prematuros, el 53,3% de género masculino; la edad gestacional promedio fue 33,4 semanas. Recibieron corticosteroides el 42%, con latencia ≥ 24 horas el 23,6% y ≥ 48 horas el 13,8%. Presentaron síndrome de dificultad respiratoria el 35% (379/1083), sepsis neonatal temprana el 4,4% (48/1083), sepsis neonatal tardía el 10,7% (116/1083), hemorragia intraventricular el 15,1% (137/908), enfermedad pulmonar crónica el 51,4% (165/321) y muerte el 22,3% (242/1083). Los corticosteroides prenatales disminuyeron el riesgo de muerte en menores de 34 semanas (OR: 0,63, IC 95%: 0,40-0,98); el decremento fue mayor si presentaron latencia ≥ 48 horas (OR: 0,40; IC 95%: 0,20-0,80). El resto de variables dependientes no se modificó por la intervención. Conclusiones: El 42% de los prematuros recibe corticosteroides prenatales. En menores de 34 semanas se observó una disminución del riesgo de muerte sin modificación en la morbilidad


Introduction: Prenatal corticosteroids reduce neonatal mortality and morbidity; however, there are few studies in developing countries, and with inconsistent results. The purpose of this study was to quantify the frequency of the use of prenatal corticosteroids and to estimate its effect on the morbidity and mortality of premature newborns. Methods: A retrospective cohort study was performed on premature newborns selected from a census conducted between January 2016 and August 2017. The use of corticosteroids was taken from the maternal records, and the dependent variables from the neonatal records. An analysis was made of the relationship using logistic regression, adjusted to gestational age and weight. Results: The study included 1083 premature infants of which 53.3% were male. The mean gestational age was 33.4 weeks. Corticosteroids were received by 42%, with latency ≥ 24 hours in 23.6% and ≥ 48 hours in 13.8%. Respiratory distress syndrome was observed in 35% (379/1083), early neonatal sepsis in 4.4% (48/1083), late neonatal sepsis in 10.7% (116/1083), intraventricular haemorrhage in 15.1% (137/908), chronic lung disease in 51.4% (165/321), and death in 22.3% (242/1083). Prenatal corticosteroids decreased the risk of death in children under 34 weeks (OR 0.63, 95% CI 0.40-0.98). The decrease was greater if they presented with latency ≥ 48 hours (OR 0.40, 95% CI 0.20-0.80). The rest of the dependent variables were not modified by the intervention. Conclusions: In preterm infants, 42% received antenatal corticosteroids. In those with less than 34 weeks, there was a decrease in the risk of death without changes in morbidity


Assuntos
Humanos , Masculino , Feminino , Gravidez , Recém-Nascido , Lactente , Glucocorticoides/administração & dosagem , Disfunção Cognitiva/etiologia , Epilepsia/complicações , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Estudos de Coortes , Idade Gestacional , Estudos de Casos e Controles , Cognição/fisiologia , Disfunção Cognitiva/sangue , Epilepsia/sangue
8.
Braz J Med Biol Res ; 52(7): e7374, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31241711

RESUMO

This study aimed to investigate the association of serum high-mobility group box-1 (HMGB1) and toll-like receptor 4 (TLR4) expressions with the risk of epilepsy as well as their correlations with disease severity and resistance to anti-epilepsy drugs. One hundred and five epilepsy patients and 100 healthy controls (HCs) were enrolled in this case-control study, and serum samples were collected from all participants to assess the HMGB1 and TLR4 expressions by enzyme-linked immunosorbent assay (ELISA). Both serum HMGB1 (P<0.001) and TLR4 (P<0.001) expressions were higher in epilepsy patients than in HCs, and they displayed good predictive values for risk of epilepsy. Moreover, HMGB1 was positively correlated with TLR4 level (r=0.735, P<0.001). HMGB1 and TLR4 levels were both elevated in patients with an average seizure duration >5 min compared to patients with a seizure duration ≤5 min (P=0.001 and P=0.014, respectively). Also, HMGB1 and TLR4 were increased in patients with seizure frequency >3 times per month compared to patients with seizure frequency ≤3 times per month (both P=0.001). In addition, HMGB1 and TLR4 expressions were higher in intractable cases compared to drug-responsive cases (P<0.001). In conclusion, both HMGB1 and TLR4 expressions were correlated with increased risk and severity of epilepsy and their level was higher in patients resistant to anti-epilepsy drugs.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/sangue , Proteína HMGB1/sangue , Receptor 4 Toll-Like/sangue , Adulto , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Epilepsia/tratamento farmacológico , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Fatores de Risco , Índice de Gravidade de Doença
9.
Basic Clin Pharmacol Toxicol ; 125(3): 215-236, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31199557

RESUMO

Anti-epileptic drugs (AEDs) have various pharmacokinetic profiles, inter-individual variabilities, high possibilities of drug-drug interactions and narrow therapeutic indices. To provide optimal treatment for patients, therapeutic drug monitoring (TDM) is necessary. However, TDM requires sufficient quantities of blood samples to measure drug concentrations. Therefore, TDM could be a burden, particularly in paediatric cases. A good alternative that overcomes these disadvantages is the dried blood spot (DBS) method, which is simple, convenient to use and less invasive, requiring a lower quantity of blood than traditional blood sampling methods. However, the DBS method is affected by haematocrit (Hct) levels to varying extents depending on the drug properties. In addition, different papers with varying characteristics are available for use when applying the DBS method. Therefore, it has not yet been applied to TDM in clinical practice. To achieve this, several steps are required, including method development, method validation and clinical validation. Currently, the development status of the DBS method is different for each AED and unclear. Therefore, we assessed the development status of the following 19 AEDs in 26 studies: lamotrigine, valproic acid, levetiracetam, phenytoin, topiramate, carbamazepine, carbamazepine epoxide, gabapentin, phenobarbital, pregabalin, clobazam, clonazepam, ethosuximide, felbamate, monohydroxycarbamazepine, nitrazepam, rufinamide, vigabatrin and zonisamide. Among them, carbamazepine, lamotrigine, topiramate and valproic acid have been developed such that they are nearly available for TDM. In addition, Whatman 903 Protein Saver Cards and concentration analysis by liquid chromatography with triple quadrupole mass spectrometer were used most often.


Assuntos
Anticonvulsivantes/uso terapêutico , Teste em Amostras de Sangue Seco/métodos , Monitoramento de Medicamentos/métodos , Epilepsia/tratamento farmacológico , Cromatografia Líquida de Alta Pressão/métodos , Epilepsia/sangue , Humanos , Espectrometria de Massas em Tandem/métodos
10.
BMC Neurosci ; 20(1): 29, 2019 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-31208341

RESUMO

BACKGROUND: Epilepsy is a common neurological disease in dogs affecting approximately 0.6-0.75% of the canine population. There is much evidence of neuroinflammation presence in epilepsy, creating new possibilities for the treatment of the disease. An increased expression of interleukin-1 beta (IL-1ß) was reported in epileptogenic foci. We hypothesized that there is an elevation of IL-1ß in serum and CSF of dogs with epilepsy, as well as in serum of dogs with TBI, reflecting involvement of this cytokine in pathophysiology of naturally occurring canine epilepsy in a clinical setting. RESULTS: IL-1ß levels were evaluated in CSF and serum of six healthy and 51 dogs with epilepsy (structural and idiopathic). In 16 dogs with TBI, only serum was tested. IL-1ß concentrations in CSF were not detectable. Serum values were not elevated in dogs with TBI in comparison to healthy controls (p > 0.05). However, dogs with epilepsy had increased levels of IL-1ß in serum (p = 0.003) regardless of the underlying cause of the disease (p = 0.0045). There was no significant relationship between the variables and IL-1ß levels. Statistically noticeable (p = 0.0630) was that approximately 10% of dog with epilepsy (R2 = 0.105) had increased seizure frequency and IL-1ß elevation. CONCLUSION: Increased IL-1ß levels were detected in the peripheral blood in dogs with idiopathic and structural epilepsy leading to the assumption that there is an involvement of inflammation in pathophysiology of epilepsy which should be considered in the search for new therapeutic strategies for this disease. However, to better understand the pathogenic role of this cytokine in epilepsy, further evaluation of IL-1ß in brain tissue is desired.


Assuntos
Lesões Encefálicas Traumáticas/veterinária , Doenças do Cão/sangue , Doenças do Cão/líquido cefalorraquidiano , Epilepsia/veterinária , Interleucina-1beta/sangue , Interleucina-1beta/líquido cefalorraquidiano , Convulsões/veterinária , Animais , Lesões Encefálicas Traumáticas/sangue , Cães , Epilepsia/sangue , Epilepsia/líquido cefalorraquidiano , Epilepsia/complicações , Feminino , Masculino , Convulsões/sangue , Convulsões/líquido cefalorraquidiano , Convulsões/complicações
11.
Pharmacology ; 104(1-2): 60-66, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31067540

RESUMO

OBJECTIVE: This study aimed to assess the population pharmacokinetics of phenytoin in Saudi patients and identify factors affecting therapeutic parameters. METHOD: A retrospective chart review was performed at King Saud University Medical City on patients treated with oral phenytoin. We used Monolix 4.4. for population pharmacokinetic modeling. A base model was developed to investigate several covariates, including age, gender, weight, total daily dose (TTD), and liver function test results. RESULTS: The analysis included a total of 81 phenytoin plasma concentrations from 43 patients (70% male). Patients' mean (± SD) age was 41 (±18.7) years and body weight was 65.4 (±17.7) kg. The patients received a phenytoin TDD of 330.5 (±104.5) mg/day, resulting in a trough concentration of 11.2 (±10.3) mg/L. The data were sufficiently described by the one-compartment open model with linear absorption and nonlinear elimination processes. Average parameter estimates for phenytoin volume of distribution (V), maximal elimination rate (Vmax), and Michaelis-Menten constant (Km) were 0.61 L/h/kg, 6.12 mg/kg/day, and 5.33 mg/L, respectively. The most significant covariates on phenytoin Vmax and Km were the age and body weight of the patients, along with valproic acid (VPA) cotherapy. CONCLUSION: The population pharmacokinetic model of phenytoin in Saudi patients found significant interindividual variability between subjects, which was affected by the patients' age, body weight, and VPA cotherapy as the most significant covariates on phenytoin Vmax and Km. To provide guidance in drug dosage decisions, further studies are required to evaluate all factors that may potentially influence the pharmacokinetics of phenytoin.


Assuntos
Anticonvulsivantes/farmacocinética , Variação Biológica da População , Epilepsia/tratamento farmacológico , Fenitoína/farmacocinética , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/administração & dosagem , Relação Dose-Resposta a Droga , Epilepsia/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Fenitoína/administração & dosagem , Estudos Retrospectivos , Arábia Saudita , Adulto Jovem
12.
Seizure ; 69: 1-6, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30947081

RESUMO

PURPOSE: To determine whether there is a relationship between the age of seizure onset and the age of menarche. METHODS: 1144 women with epilepsy (WWE) in the community, ages 18-47 years, provided web-based survey data. We compared the frequencies of the individual differences between their ages of seizure onset and menarche to each other and chance. We determined whether the age of menarche is a predictor of the age of seizure onset and the percentage of the variance that menarche explains. We used two-step cluster analysis to auto-identify a cluster of years relative to the age of menarche that showed the greatest predilection for seizure onset. RESULTS: Average age of menarche was 12.55 [95% CI: 12.45-12.65]. It was greater in WWE who developed seizures before versus after menarche (12.70 [12.54-12.86] v 12.42 [12.30-12.54], p = 0.006). More WWE had seizure onset during the year of menarche than during any other year (8.3% v expected 2.1%; p < 0.0001). Menarche, however, explained only 1% of the variance. Seizure onset frequencies were greatest for an auto-identified cluster that spanned 2 years before to 6 years after menarche and subsumed 49.3% of seizure onset. CONCLUSION: Although the results indicate a significant relationship between the age of seizure onset and the age of menarche, the broader auto-identified perimenarchal cluster that subsumes 49.3% of seizure onset suggests that research target the potential role of the great increase in adrenarchal, as well as gonadarchal, neuroactive steroids that modulate neuronal excitability and seizures during that span.


Assuntos
Idade de Início , Epilepsia/sangue , Menarca/sangue , Convulsões/sangue , Adolescente , Adulto , Distribuição por Idade , Feminino , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
13.
Seizure ; 67: 18-22, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30852267

RESUMO

PURPOSE: To investigate the correlation between steady-state plasma concentrations of perampanel (PER) with efficacy and tolerability in adult patients with difficult-to-treat epilepsy. METHODS: PER plasma concentrations were assessed at steady-state conditions in 92 adult patients (57% female, 43% male, mean age 39,5 years, age range 20-73 years). All patients had been treated with PER at a stable dose for at least 3 weeks. Clinical efficacy was assessed on the day of measuring the plasma concentrations by a retrospective analysis of the seizure frequency and adverse effects. RESULTS: The mean overall plasma concentration was 323,5 ng/ml (range 19 ng/ml - 2436 ng/ml). The corresponding mean dose was 7,5 mg (range 2 mg - 12 mg). PER dose and plasma concentration showed a close linear correlation. Plasma levels and doses varied widely concerning both efficacy and tolerability of PER. The differences between plasma levels of responders and non-responders were not statistically significant. Therefore a clinically useful general reference range could not be defined. CONCLUSION: Our data do not indicate a reliable therapeutic range for PER plasma concentrations. Individual reference ranges varied widely. Therapeutic drug monitoring (TDM) may still be helpful in certain clinical situations.


Assuntos
Anticonvulsivantes/sangue , Anticonvulsivantes/uso terapêutico , Epilepsia/sangue , Epilepsia/tratamento farmacológico , Piridonas/sangue , Piridonas/uso terapêutico , Adulto , Idoso , Anticonvulsivantes/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piridonas/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
14.
Epilepsy Res ; 152: 1-6, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30852339

RESUMO

BACKGROUND: Body weight (BW) gain may be induced by perampanel (PER) administration, similar to the well-known adverse effects of valproic acid and gabapentin. Intellectual disability (ID) and serum PER concentration may be risk factors of BW gain. PURPOSE: This study investigated how ID and serum PER concentration are associated with PER-induced BW gain. METHODS: Subjects were 76 patients with epilepsy (41 men, aged 16-70 years). All patients were divided by intelligence quotient (IQ) into no ID (IQ ≥ 70, n = 24), mild to moderate ID (70 > IQ ≥35, n = 31), and severe to profound ID (IQ < 35, n = 21) groups. BW was measured before and 2, 4, 6, and 12 months after initiation of PER treatment, and serum PER concentration at 12 months. RESULTS: BW gains in the mild to moderate ID group at 4, 6, and 12 months were significantly (p < 0.05) higher than in the no ID and in the severe to profound ID groups. At 12 months, BW gain was associated with serum PER concentrations in the no ID (p = 0.034) and the mild to moderate ID (p = 0.001) groups but not in the severe to profound ID group. Multiple linear regression analysis found BW gain at 12 months was positively correlated with the mild to moderate ID group (ß = 0.373, p = 0.002) and serum PER concentration (ß = 0.241, p = 0.047). CONCLUSIONS: The mild to moderate ID group gained more BW than the no ID group, suggesting that PER-induced food intake was greater due to weaker behavioral control in the mild to moderate ID group. The present study suggests a linear correlation between serum PER concentration and BW change.


Assuntos
Anticonvulsivantes/sangue , Deficiência Intelectual/sangue , Piridonas/sangue , Ganho de Peso/efeitos dos fármacos , Adolescente , Adulto , Idoso , Epilepsia/sangue , Epilepsia/tratamento farmacológico , Feminino , Seguimentos , Humanos , Deficiência Intelectual/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores de Tempo , Adulto Jovem
15.
Epilepsy Res ; 153: 7-13, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30925397

RESUMO

BACKGROUND AND AIMS: The relationship between anti-epileptic usage and oxidative damage has not yet been clearly understood. In our study, we investigated oxidative stress parameters, carnitine levels, liver function tests (LFT) and their relationship in epileptic children treated with valproic acid or levetiracetam. METHOD: LFTs, serum free carnitine and oxidative damage markers and their relations with each other were determined in patients who are on valproic acid or levetiracetam treatment at least for 6 months. 25 patients on therapeutic doses of valproic acid, 26 patients on therapeutic doses of levetiracetam and 26 healthy volunteers as controls were included. LFTs, ammonia, carnitine, lipid peroxidation biomarker malondialdehyde (MDA) and a sensitive marker of DNA damage, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were measured. Results of patients are compared to healthy controls. The data is evaluated with IBM SPSS Statistics 22.0. RESULTS: Ammonia and MDA levels were elevated in patients using levetiracetam; 8-OHdG levels were elevated in both patient groups. Carnitine levels were significantly low in patients under valproic acid therapy, however they were not found to be correlated with MDA, 8-OHdG or LFTs. MDA showed positive correlation with ammonia and 8-OHdG in the levetiracetam group. CONCLUSION: We did not observe hepatotoxicity in patients under therapeutic doses of valproic acid. However, epileptic children under therapeutic doses of levetiracetam showed significantly elevated levels of MDA and 8-OHdG, which is supportive for oxidative damage under levetiracetam therapy. This result was observed for the first time in childhood epilepsies and further studies are needed to understand its mechanism.


Assuntos
Carnitina/sangue , Epilepsia/tratamento farmacológico , Levetiracetam/efeitos adversos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Ácido Valproico/efeitos adversos , Anticonvulsivantes , Criança , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Epilepsia/sangue , Feminino , Humanos , Testes de Função Hepática , Masculino , Malondialdeído/metabolismo , Estudos Retrospectivos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
16.
Artigo em Inglês | MEDLINE | ID: mdl-30834829

RESUMO

BACKGROUND: Epilepsy is a serious clinical condition characterized by recurrent seizures. Oxidative stress plays an important role in the etio-pathogenesis of epilepsy. Measurements of serum thiol and disulfide levels were used to evaluate the antioxidant status of the body. OBJECTIVE: The aim of this study was to determine serum levels of thiol and disulfide in epileptic pediatric patients. METHODS: Ninety patients, 54 epilepsy and 36 controls were included in the study. Serum levels of native thiol total thiol and disulfide were measured and disulfide/native, disulfide / total thiol and native thiol/ total thiol ratios were calculated. Hence, the ratios of disulfide/ native thiol, disulfide / total thiol and native thiol/ total thiol were calculated. RESULTS: Serum levels of native thiol, total thiol and disulfide were significantly lower in the epilepsy group than the control group. The ratio of disulfide/native thiol and disulfide / total thiol were significantly higher in the study group than the control group. As well as, the native thiol / total thiol ratio was lower in the epilepsy group than the control group. Native thiol, total thiol and disulfide were significantly lower in the epilepsy group who were taking anti-epileptic drugs than those who were not taking anti-epileptic drugs. CONCLUSION: We demonstrated a meaningful relationship between oxidative stress markers and epilepsy in pediatric patients.


Assuntos
Dissulfetos/sangue , Epilepsia/sangue , Compostos de Sulfidrila/sangue , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Prospectivos
17.
Niger J Clin Pract ; 22(2): 186-193, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30729941

RESUMO

Background: Alteration in the homeostasis of trace elements such as magnesium may play a role in the development of epileptic seizures. This study aims to investigate the levels of serum magnesium in people with idiopathic generalized epileptic (IGE) seizures and symptomatic seizures in Northeast Nigeria. Materials and Methods: Serum magnesium level was measured using atomic absorption spectrometry among 40 adults with IGE, 20 adults with symptomatic epileptic seizures, and 30 healthy controls. Serum calcium, potassium, phosphate, and albumin were also measured. Results: The mean serum magnesium level was significantly lower among people with epilepsy compared with the controls [0.79 ± 0.18 mmol/L vs 0.90 mmol/L ± 0.17, P = 0.007, 95% confidence interval (CI): (-0.189 to -0.031)]. People with IGE had significantly lower levels of magnesium compared with those with symptomatic seizures [0.74 ± 0.17 mmol/L vs 0.9 ± 0.16 mmol/L, P < 0.001 95% CI: (-0.251 to -0.069)]. The mean magnesium level for all groups was in the reference range, but the lowest levels were observed in those with IGE. There is no significant correlation between the level of serum magnesium and the severity of seizure attacks. There was significantly lower level of calcium in people with IGE compared with those with symptomatic seizures [2.3 ± 0.13 mmol/L vs 2.4 ± 0.16 mmol/L, P = 0.012, 95% CI: (-0.177 to 0.023)] or controls [2.3 ± 0.13 mmol/L vs 2.4 ± 0.12 mmol/L, P < 0.01, 95% CI: (-0.156 to -0.044)]. No significant differences were observed in the levels of potassium, phosphate, and albumin. Conclusion: This study suggests that low serum magnesium and calcium may play a role in IGE, and supplementation may be useful in reducing seizures in Black patients with epilepsy.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Magnésio/sangue , Convulsões/tratamento farmacológico , Adolescente , Adulto , Albuminas/metabolismo , Cálcio/sangue , Estudos Transversais , Epilepsia/sangue , Epilepsia/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Fosfatos/sangue , Potássio/sangue , Convulsões/sangue , Convulsões/epidemiologia , Espectrofotometria Atômica , Adulto Jovem
18.
Neurol Res ; 41(4): 378-383, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30739590

RESUMO

OBJECTIVES: We attempted to determine whether a functional polymorphism of TRPM6 (rs2274924) is associated with susceptibility to epilepsy following ischemic stroke, and to further explore the effect of this polymorphism on serum levels of Mg2+ in post-stroke patients. METHODS: We carried out a case-control study on 378 post-stroke epilepsy patients and 420 controls (stroke patients without secondary epilepsy). We used DNA sequencing to determine the genotypes of the TRPM6 rs2274924 polymorphism, and used the ion selective electrode method to measure serum levels of Mg2+. RESULTS: The distribution of the CC genotype and the frequency of the C allele were significantly higher in the post-stroke epilepsy patients than in the controls (P < 0.01). With regard to the post-stroke epilepsy patients, the serum levels of Mg2+ decreased significantly in the TRPM6 rs2274924 C allele carriers compared to the rs2274924 T allele carriers. CONCLUSION: The TRPM6 rs2274924 polymorphism may be associated with susceptibility to epilepsy following stroke, and the C allele may be associated with increased risk of post-stroke epilepsy. The TRPM6 rs2274924 polymorphism may also influence serum levels of Mg2+ in post-stroke epilepsy patients.


Assuntos
Epilepsia/etiologia , Epilepsia/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Acidente Vascular Cerebral/complicações , Canais de Cátion TRPM/genética , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , Epilepsia/sangue , Epilepsia/fisiopatologia , Feminino , Estudos de Associação Genética , Humanos , Magnésio , Masculino
19.
Artigo em Inglês | MEDLINE | ID: mdl-30660838

RESUMO

Carbamazepine (CBZ) was considered as the drug of choice in the treatment for various forms of epilepsy, yet the non-negligible adverse effects of CBZ suspend as the major concern for rational and efficient clinical medication. This study developed a method for the simultaneous determination of CBZ and its seven metabolites acridine (AI), iminostilbene (IM), acridone (AO), carbamazepine­10,11­epoxide (CBZ­EP), 10,11­dihydro­10,11­trans­dihy­droxy­carbamazepine (CBZ­DiOH), 2­hydroxycarbamazepine (2­OH­CBZ) and 3­hydroxycarbamazepine (3­OH­CBZ) with phenacetin as the internal standard (IS) using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Plasma samples were purified with the one-step 96-well protein precipitation plate. Chromatographic separation was achieved on an Agilent Eclipse XDB-C18 (1.8 µm, 2.1 mm × 50 mm) chromatography column carrying the mobile phrase of acetonitrile and 0.1% formic acid in a gradient elution at a flow rate 0.3 mL/min. Agilent G6460 MS/MS in the positive MRM mode using electrospray ionization (ESI) was applied for quantification of target compounds. CBZ and its seven metabolites showed good linear correlation coefficient (r > 0.990). Intra-day and inter-day precision (CV) were no >15%. This method was successfully accomplished within 5 min which was especially applicable for therapeutic drug monitoring (TDM) of CBZ and its metabolites in epileptic patients, and it provided insights for toxicological studies to achieve a rational and effective individualized administration in clinical practice.


Assuntos
Carbamazepina/sangue , Dibenzazepinas/sangue , Epilepsia/sangue , Acridinas , Cromatografia Líquida de Alta Pressão , Monitoramento de Medicamentos , Humanos , Metaboloma , Espectrometria de Massas em Tandem
20.
An Pediatr (Barc) ; 91(2): 88-95, 2019 Aug.
Artigo em Espanhol | MEDLINE | ID: mdl-30660389

RESUMO

INTRODUCTION: Cognitive impairment is a common consequence of epilepsy in children. This study aimed to assess the ratio of omega-6 to omega-3 fatty acid levels and its impact on cognitive function in children with idiopathic epilepsy. PATIENTS AND METHODS: We performed a case-control study in 30 children with idiopathic epilepsy and 20 healthy children. We measured levels of alpha-linolenic acid (omega-3) and linoleic acid (omega-6) by means of gas-liquid chromatography. We assessed cognitive function with the Arabic version of the fourth edition of the Stanford-Binet test and the P300 component of event-related potentials. All children had an intelligent quotient greater than 70. RESULTS: Children with epilepsy had lower levels of omega-3 and higher levels of omega-6 fatty acids and an abnormal omega-6/omega-3 ratio compared to non-epileptic children. We found a significant positive correlation of serum omega-3 levels and a significant negative correlation of serum omega-6 levels with cognitive function scores and P300 latency in children with epilepsy. CONCLUSION: Children with epilepsy have abnormal ratios of omega-6 to omega-3 fatty acid serum levels, which is associated with impaired cognitive function in these children.


Assuntos
Disfunção Cognitiva/etiologia , Epilepsia/complicações , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Cognição/fisiologia , Disfunção Cognitiva/sangue , Epilepsia/sangue , Feminino , Humanos , Masculino
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