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1.
Neurol Neurochir Pol ; 55(5): 429-439, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34541635

RESUMO

INTRODUCTION: Vigabatrin (VGB), a second-generation antiepileptic drug, is effective for the treatment of infantile spasms and focal seizures, primarily in tuberous sclerosis complex (TSC) patients. However, reports of adverse events of VGB, including VGB-associated visual field loss and brain abnormalities in neuroimaging, have raised concerns about the broader use of VGB and thus significantly limited its application. AIM OF THE STUDY: The goal of this review was to summarise the recent therapeutic guidelines, the use of VGB in focal seizures and new VGB applications as a disease-modifying treatment in TSC patients. Moreover, we discuss the current opinions on potential VGB-associated toxicity and the safety of VGB.


Assuntos
Epilepsia , Espasmos Infantis , Esclerose Tuberosa , Anticonvulsivantes/efeitos adversos , Criança , Epilepsia/tratamento farmacológico , Humanos , Espasmos Infantis/tratamento farmacológico , Esclerose Tuberosa/tratamento farmacológico , Vigabatrina/efeitos adversos
2.
Seizure ; 91: 503-506, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34371246

RESUMO

Vigabatrin (VGB) is approved as monotherapy for pediatric patients with Infantile Spasms (IS). Duration of VGB use should be limited because of the risk of retinal and neurotoxicity, but the optimal length of treatment is unknown. Our study aimed to determine the risk of spasms relapse after 6 months of VGB as first-line therapy in IS patients deemed VGB good responders. The participants were 44 infants with IS who demonstrated both absence of clinical spasms and hypsarrhythmia four weeks after starting VGB, obtained from two cohorts: 29 patients from a multicenter prospective cohort and 15 patients from a retrospective single-center cohort. We divided them post hoc into two groups according to the duration of VGB treatment: 6-month group (n=34) and >6-month group (n=10) and compared outcome between the two groups. No patient in either group had a relapse of spasms. For patients with non-identified etiology (NIE) in the 6 months treatment group, no other seizure types were observed. Late epilepsy, in the form of focal seizures, emerged in only 5/37 patients (3/30 in the 6-month treatment group; 2/7 in the extended treatment group); all within the first 6-9 months after VGB initiation. Our study provides substantial evidence that a shortened VGB course of 6 months could be sufficient to treat and prevent relapse of spasms in children with IS, particularly those with NIE.


Assuntos
Espasmos Infantis , Vigabatrina , Anticonvulsivantes/efeitos adversos , Criança , Humanos , Lactente , Estudos Prospectivos , Estudos Retrospectivos , Espasmo/tratamento farmacológico , Espasmos Infantis/tratamento farmacológico , Resultado do Tratamento , Vigabatrina/efeitos adversos
3.
Artigo em Inglês | MEDLINE | ID: mdl-34348203

RESUMO

Mixed-mode chromatography-comprising a mixed phase with reversed and ionic phases, enabling hydrophobic and ion-exchange interactions simultaneously-was applied to identify vigabatrin enantiomers by HPLC with pre-column fluorescence derivatization with 2,5-dioxopyrrolidin-1-yl (4-(((2-nitrophenyl)sulfonyl)oxy)-6-(3-oxomorpholino)quinoline-2-carbonyl)prolinate (Ns-MOK-(S)-Pro-OSu). The MOK-(S)-Pro-vigabatrin enantiomers were efficiently separated within 12 min (total analysis time per sample: 28 min, including washing and equilibrium time for the column). The mobile phase was H2O/CH3OH/10 mM ammonium formate (pH 2.0) (20/20/60, v/v/v). Column temperature was maintained at 60℃. The proposed HPLC method could successfully monitor plasma vigabatrin enantiomer levels in rats administered (±)-vigabatrin (50 mg/kg, p.o.).


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Vigabatrina , Animais , Limite de Detecção , Modelos Lineares , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Estereoisomerismo , Vigabatrina/sangue , Vigabatrina/química , Vigabatrina/isolamento & purificação
4.
J Pediatr Ophthalmol Strabismus ; 58(3): 174-179, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34039156

RESUMO

PURPOSE: To determine changes in the clinical treatment of pediatric patients taking vigabatrin for seizure control in response to results of electroretinogram (ERG) performed for retinal toxicity screening. METHODS: The authors retrospectively reviewed the medical records of patients who received ERGs at Children's Hospital of Colorado from 2009 to 2012. Age, indication for ERG, ERG data, and clinical management of vigabatrin were extracted from the records. ERGs were interpreted according to LKC Technologies normative values. A physician trained in ERG analysis interpreted each ERG. RESULTS: One hundred seventy ERGs were performed during the study period, and 147 ERGs were available for analysis. Every patient received general anesthesia for the procedure. Thirty-three ERGs were performed in 29 patients specifically as screening for retinal toxicity due to vigabatrin use, and 30 were available for analysis. Within this cohort, only 2 ERGs were normal (6.6%), and 28 were abnormal (93.3%). In patients who received abnormal results, 1 patient discontinued vigabatrin in response to the screening. CONCLUSIONS: In this study cohort, clinical management generally did not change in response to an abnormal screening result. Given the need for general anesthesia in the pediatric population receiving ERG testing, and minimal change in clinical decision-making in the face of abnormal results, ERG screening for retinal toxicity due to vigabatrin in the pediatric cohort should be reconsidered. [J Pediatr Ophthalmol Strabismus. 2021;58(3):174-179.].


Assuntos
Anticonvulsivantes , Vigabatrina , Anticonvulsivantes/efeitos adversos , Criança , Eletrorretinografia , Humanos , Retina , Estudos Retrospectivos , Vigabatrina/efeitos adversos
5.
J Pharm Biomed Anal ; 201: 114110, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33971590

RESUMO

Recently, charged aerosol detection (CAD), a universal detection technique in liquid chromatography, has been introduced into monographs of the European Pharmacopoeia (Ph. Eur.), which now employs HPLC-UV-CAD for assessing the impurities of the drug vigabatrin. The separation of vigabatrin and its impurities is facilitated by ion pair chromatography (IPC) in the compendial method using tridecafluoroheptanoic acid (TDFHA) as ion-pairing reagent. However, the subsequent detection of the impurities by UV-CAD is considerably impaired due to the substantial amount of ion-pairing reagent applied in the method generating high levels of background noise. In this study, the influence of the mobile phase composition on the background noise of the CAD was evaluated applying response surface methodology. The model's results indicated that the chain length of the ion-pairing reagent is a predominant factor for noise generation. Thus, an alternative method for the impurity analysis of vigabatrin using mixed-mode chromatography (MMC) instead of IPC was developed. The dual separation mechanism of the MMC column enabled the choice of a mobile phase better suited for the individual requirements of the UV-CAD detectors, while maintaining excellent selectivity. The MMC method does not require the addition of a post-column solution to reduce the TDFHA concentration in the mobile phase, and, therefore, needs less instrumentation. Moreover, the sample concentration could be halved due to the improved LOQs of the impurities (<50 ng on column) and the analysis time could be shortened (30 to 20 min) due to improved separation efficiency. The MMC method was validated with respect to ICH guideline Q2(R1).


Assuntos
Vigabatrina , Aerossóis , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida
6.
Epilepsia ; 62(7): 1656-1664, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34008866

RESUMO

OBJECTIVE: It has been known that West syndrome (WS) patients with an unknown etiology have better clinical outcomes than patients with an identified etiology of any kind. However, after the exponential discovery of genes with mutations responsible for developmental and epileptic encephalopathy (DEE), a significant proportion of patients with a previously unknown etiology have been reclassified as having a genetic etiology, requiring reinvestigation of this concept. Therefore, this study investigated clinical outcomes of WS patients with genetic and unknown etiologies. METHODS: Patients diagnosed with WS without structural or metabolic abnormalities were included in this study. The DEE gene panel, comprising 172 genes, was performed for all patients. All patients were treated using the same treatment protocol for vigabatrin and high-dose prednisolone add-on therapy. Favorable responders were defined as patients who were seizure-free and whose electroencephalogram showed Burden of Amplitudes and Epileptiform Discharges scores of 2 or less. RESULTS: Of the 58 patients included in the study, 17 (29.3%) patients had an identified genetic etiology. There was no significant difference in rates of favorable response at 1 and 3 months after treatment, but significantly higher proportions of patients exhibited favorable responses among those with an unknown etiology at long-term follow-up (41.2% vs. 78.0%, p = .006 at 6 months; 29.4% vs. 65.9%, p = .011 at 1 year; 23.5 vs. 65.9%, p = .003 at 2 years). Moreover, the mental, psychomotor, and social age quotients of the patients with an identified genetic etiology were reduced to a significantly greater degree since diagnosis compared with those of the patients with an unknown etiology. SIGNIFICANCE: WS patients with genetic and unknown etiologies did not initially exhibit significantly different response rates to the vigabatrin and high-dose prednisolone add-on treatment. However, patients with a genetic etiology exhibited significantly higher relapse rates and significantly poorer long-term responses.


Assuntos
Espasmos Infantis/tratamento farmacológico , Espasmos Infantis/genética , Idade de Início , Anti-Inflamatórios/uso terapêutico , Anticonvulsivantes/uso terapêutico , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/etiologia , Criança , Pré-Escolar , Quimioterapia Combinada , Eletroencefalografia , Feminino , Seguimentos , Estudo de Associação Genômica Ampla , Humanos , Lactente , Masculino , Testes Neuropsicológicos , Prednisolona/uso terapêutico , Espasmo/tratamento farmacológico , Espasmo/etiologia , Espasmos Infantis/psicologia , Resultado do Tratamento , Vigabatrina/uso terapêutico
7.
J Radiol Case Rep ; 15(2): 1-6, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33717406

RESUMO

Vigabatrin therapy is commonly used in infants diagnosed with tuberous sclerosis complex, particularly in the setting of epilepsy. Utilization of vigabatrin can result in bilateral and symmetric abnormal sequence changes within the deep brain matter and brainstem on magnetic resonance imaging. These abnormalities occur predominantly in infancy, are reversible, and can be asymptomatic or result in symptomatic clinical manifestations. We present a case with classic neuroimaging findings. Familiarity with these findings can prevent unnecessary follow up tests or studies and the cost of continuing or discontinuing vigabatrin therapy should be weighed heavily against the potential manifestation of extrapyramidal symptoms.


Assuntos
Esclerose Tuberosa/diagnóstico por imagem , Esclerose Tuberosa/tratamento farmacológico , Vigabatrina/efeitos adversos , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino
8.
Epilepsia ; 62(5): 1208-1219, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33778971

RESUMO

OBJECTIVE: To study the association between timing and characteristics of the first electroencephalography (EEG) with epileptiform discharges (ED-EEG) and epilepsy and neurodevelopment at 24 months in infants with tuberous sclerosis complex (TSC). METHODS: Patients enrolled in the prospective Epileptogenesis in a genetic model of epilepsy - Tuberous sclerosis complex (EPISTOP) trial, had serial EEG monitoring until the age of 24 months. The timing and characteristics of the first ED-EEG were studied in relation to clinical outcome. Epilepsy-related outcomes were analyzed separately in a conventionally followed group (initiation of vigabatrin after seizure onset) and a preventive group (initiation of vigabatrin before seizures, but after appearance of interictal epileptiform discharges [IEDs]). RESULTS: Eighty-three infants with TSC were enrolled at a median age of 28 days (interquartile range [IQR] 14-54). Seventy-nine of 83 patients (95%) developed epileptiform discharges at a median age of 77 days (IQR 23-111). Patients with a pathogenic TSC2 variant were significantly younger (P-value .009) at first ED-EEG and more frequently had multifocal IED (P-value .042) than patients with a pathogenic TSC1 variant. A younger age at first ED-EEG was significantly associated with lower cognitive (P-value .010), language (P-value .001), and motor (P-value .013) developmental quotients at 24 months. In the conventional group, 48 of 60 developed seizures. In this group, the presence of focal slowing on the first ED-EEG was predictive of earlier seizure onset (P-value .030). Earlier recording of epileptiform discharges (P-value .019), especially when multifocal (P-value .026) was associated with higher risk of drug-resistant epilepsy. In the preventive group, timing, distribution of IED, or focal slowing, was not associated with the epilepsy outcomes. However, when multifocal IEDs were present on the first ED-EEG, preventive treatment delayed the onset of seizures significantly (P-value <.001). SIGNIFICANCE: Early EEG findings help to identify TSC infants at risk of severe epilepsy and neurodevelopmental delay and those who may benefit from preventive treatment with vigabatrin.


Assuntos
Anticonvulsivantes/uso terapêutico , Diagnóstico Precoce , Epilepsia/diagnóstico , Epilepsia/tratamento farmacológico , Esclerose Tuberosa/complicações , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/etiologia , Eletroencefalografia , Epilepsia/etiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Esclerose Tuberosa/diagnóstico , Esclerose Tuberosa/genética , Proteína 1 do Complexo Esclerose Tuberosa/genética , Proteína 2 do Complexo Esclerose Tuberosa/genética , Vigabatrina/uso terapêutico
9.
Neurosciences (Riyadh) ; 26(1): 21-25, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33530039

RESUMO

OBJECTIVES: To assess the neurodevelopmental and epilepsy outcomes in children with infantile spasms (IS). METHODS: A retrospective chart review of all patients with infantile spasms admitted to King Khalid University Hospital (KKUH), Riyadh, Saudi Arabia between January 2000 and December 2017. Infants who were diagnosed to have IS as per the International League Against Epilepsy (ILAE) definition were included in this study. Patients who lost follow-up and those who did not receive treatment at KKUH were excluded. RESULTS: Total of 53 patients were included and categorized into unknown, cryptogenic and symptomatic type of IS. The majority had symptomatic etiology (71.7%). Type of etiology and delay in initiation of treatment were significant predictors of motor and cognitive outcomes, but not seizure control. Patients with unknown IS, who were diagnosed earlier (0.72-month), had better neurodevelopmental outcomes. Vigabatrin in combination with either Adrenocorticotropic hormone (ACTH) or Prednisolone showed better seizure control in comparison to monotherapy and other combination modalities. CONCLUSION: Neurodevelopmental outcomes of IS are strongly associated with the underlying etiology. Early initiation of treatments had a favorable cognitive and motor outcome. Early response to combination therapy with resolution of spasms and hypsarrhythmia had better seizure outcomes. However, motor and cognitive outcomes were not affected by the response to the combination therapy.


Assuntos
Hormônio Adrenocorticotrópico/uso terapêutico , Anticonvulsivantes/uso terapêutico , Prednisolona/uso terapêutico , Espasmos Infantis/tratamento farmacológico , Vigabatrina/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Arábia Saudita , Centros de Atenção Terciária , Resultado do Tratamento
10.
Epilepsia ; 62(2): 285-302, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33426641

RESUMO

The safety of switching between generic products of antiseizure medications (ASMs) continues to be a hot topic in epilepsy management. The main reason for concern relates to the uncertainty on whether, and when, two generics found to be bioequivalent to the same brand (reference) product are bioequivalent to each other, and the risk of a switch between generics resulting in clinically significant changes in plasma ASM concentrations. This article addresses these concerns by discussing the distinction between bioequivalence and statistical testing for significant difference, the importance of intra-subject variability in interpreting bioequivalence studies, the stricter regulatory bioequivalence requirements applicable to narrow-therapeutic-index (NTI) drugs, and the extent by which currently available generic products of ASMs comply with such criteria. Data for 117 oral generic products of second-generation ASMs approved in Europe by the centralized, mutual recognition or decentralized procedure were analyzed based on a review of publicly accessible regulatory assessment reports. The analysis showed that for 99% of generic products assessed (after exclusion of gabapentin products), the 90% confidence intervals (90% CIs) of geometric mean ratios (test/reference) for AUC (area under the drug concentration vs time curve) were narrow and wholly contained within the acceptance interval (90%-111%) applied to NTI drugs. Intra-subject variability for AUC was <10% for 53 (88%) of the 60 products for which this measure was reported. Many gabapentin generics showed broader, 90% CIs for bioequivalence estimates, and greater intra-subject variability, compared with generics of other ASMs. When interpreted within the context of other available data, these results suggest that any risk of non-bioequivalence between these individual generic products is small, and that switches across these products are not likely to result in clinically relevant changes in plasma drug exposure. The potential for variability in exposure when switching across generics is likely to be greatest for gabapentin.


Assuntos
Anticonvulsivantes/farmacocinética , Equivalência Terapêutica , Área Sob a Curva , Variação Biológica Individual , Dibenzazepinas/farmacocinética , Substituição de Medicamentos , Medicamentos Genéricos , Europa (Continente) , Gabapentina/farmacocinética , Humanos , Lacosamida/farmacocinética , Lamotrigina/farmacocinética , Levetiracetam/farmacocinética , Oxcarbazepina/farmacocinética , Pregabalina/farmacocinética , Topiramato/farmacocinética , Vigabatrina/farmacocinética , Zonisamida/farmacocinética
11.
Ann Neurol ; 89(2): 304-314, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33180985

RESUMO

OBJECTIVE: Epilepsy develops in 70 to 90% of children with tuberous sclerosis complex (TSC) and is often resistant to medication. Recently, the concept of preventive antiepileptic treatment to modify the natural history of epilepsy has been proposed. EPISTOP was a clinical trial designed to compare preventive versus conventional antiepileptic treatment in TSC infants. METHODS: In this multicenter study, 94 infants with TSC without seizure history were followed with monthly video electroencephalography (EEG), and received vigabatrin either as conventional antiepileptic treatment, started after the first electrographic or clinical seizure, or preventively when epileptiform EEG activity before seizures was detected. At 6 sites, subjects were randomly allocated to treatment in a 1:1 ratio in a randomized controlled trial (RCT). At 4 sites, treatment allocation was fixed; this was denoted an open-label trial (OLT). Subjects were followed until 2 years of age. The primary endpoint was the time to first clinical seizure. RESULTS: In 54 subjects, epileptiform EEG abnormalities were identified before seizures. Twenty-seven were included in the RCT and 27 in the OLT. The time to the first clinical seizure was significantly longer with preventive than conventional treatment [RCT: 364 days (95% confidence interval [CI] = 223-535) vs 124 days (95% CI = 33-149); OLT: 426 days (95% CI = 258-628) vs 106 days (95% CI = 11-149)]. At 24 months, our pooled analysis showed preventive treatment reduced the risk of clinical seizures (odds ratio [OR] = 0.21, p = 0.032), drug-resistant epilepsy (OR = 0.23, p = 0.022), and infantile spasms (OR = 0, p < 0.001). No adverse events related to preventive treatment were noted. INTERPRETATION: Preventive treatment with vigabatrin was safe and modified the natural history of seizures in TSC, reducing the risk and severity of epilepsy. ANN NEUROL 2021;89:304-314.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/prevenção & controle , Esclerose Tuberosa/fisiopatologia , Vigabatrina/uso terapêutico , Epilepsia Resistente a Medicamentos/prevenção & controle , Eletroencefalografia , Epilepsia/tratamento farmacológico , Epilepsia/etiologia , Epilepsia/fisiopatologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Programas de Rastreamento , Convulsões/diagnóstico , Convulsões/tratamento farmacológico , Convulsões/etiologia , Convulsões/prevenção & controle , Espasmos Infantis/prevenção & controle , Esclerose Tuberosa/complicações
12.
J Sleep Res ; 30(3): e13137, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32657499

RESUMO

Synaptic downscaling during sleep, a physiological process to restore synaptic homeostasis and maintain learning efficiency and healthy brain development, has been related to a reduction of the slope of sleep slow waves (SSW). However, such synaptic downscaling seems not to be reflected in high-amplitude SSW. Recently we have shown reduced SSW slopes during hormonal treatment (adrenocorticotrophic hormone, prednisolone) in patients with West syndrome (WS). Yet, whether this reduction was related to successful treatment or reflects a specific effect of hormone therapy is unknown. Thus, we retrospectively analysed nap electroencephalograms of 61 patients with WS successfully treated with hormones, vigabatrin (VGB), or both. The slope of SSW during treatment (T1) and 2-7 months later (T2) when hormonal treatment was tapered off were compared between the treatment groups and healthy, age-matched controls. At T1 hormone treatment reduced the slope of low-amplitude SSW, whereas VGB increased the slope of high-amplitude SSW (linear mixed effect model: FGroup  = 7.04, p < 0.001; FAmplitude  = 1,646.68, p < 0.001; FGroup*Amplitude  = 3.38, p < 0.001). At T2, untreated patients did not differ anymore from healthy controls, whereas those still under VGB showed the same alterations as those with VGB at T1. This result indicates a disparate effect of VGB and hormone on the SSW slope. In particular, hormones seem to reduce the slope of cortical generated low-amplitude SSW, similar to the physiological synaptic downscaling during sleep. Thus, a loss of functional neuronal connectivity might be an alternative explanation of the antiepileptic effect of hormonal treatment.


Assuntos
Anticonvulsivantes/uso terapêutico , Eletroencefalografia/métodos , Hormônios/análise , Sono de Ondas Lentas/efeitos dos fármacos , Vigabatrina/efeitos adversos , Anticonvulsivantes/farmacologia , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Estudos Retrospectivos , Espasmos Infantis/induzido quimicamente , Espasmos Infantis/tratamento farmacológico , Espasmos Infantis/fisiopatologia , Síndrome
13.
Epilepsy Behav ; 114(Pt A): 107235, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32694038

RESUMO

OBJECTIVE: We describe the electroclinical characteristics of a series of 26 patients with idiopathic West syndrome (WS), who had an excellent response to treatment with vigabatrin (VGB) and corticosteroids alone or in combination. METHODS: Evaluating the records of 178 patients with WS studied at Garrahan Hospital, Niño Jesús Hospital, and Clínica San Lucas between January 2005 and June 2017, we selected 26 patients that met the inclusion criteria of idiopathic WS. The inclusion criteria for idiopathic WS were (1) no personal history of disease, (2) normal neurological examination and neurodevelopment, (3) symmetric spasms in clusters not preceded by any other type of seizure, (d) symmetric hypsarrhythmia, (e) normal electroencephalogram (EEG) background, e.g., normal sleep EEG pattern, (f) normal magnetic resonance imaging (MRI) recording, (g) normal neurometabolic and genetic studies, and (h) at least 2 years of follow-up. RESULTS: Fifteen boys and 11 girls met the inclusion criteria of idiopathic WS. The current age of the children ranges between 2 years 10 months and 12 years 10 months. Age at first epileptic spasms (ES) ranged from 4 to 11 months, with a mean age of 7 and a median of 7.5 months, respectively; ES were in clusters, bilateral and symmetrical in all cases. Spasms were flexor in nine (34.7%), mixed flexor-extensor in 15 (57.7%), and extensor in three (7.6%). In all patients the EEG showed typical pattern of hypsarrhythmia. CONCLUSION: These patients with idiopathic WS who have an excellent response to initial treatment should be treated for a short period of time with adrenocorticotropic hormone (ACTH) and VGB alone or in combination.


Assuntos
Espasmos Infantis , Hormônio Adrenocorticotrópico , Criança , Eletroencefalografia , Feminino , Humanos , Lactente , Masculino , Convulsões , Espasmos Infantis/tratamento farmacológico , Resultado do Tratamento , Vigabatrina
14.
Biomed Chromatogr ; 35(5): e5060, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33377241

RESUMO

Herein, determination of an antiepileptic drug, (±)-vigabatrin (VB), was performed by reversed-phase HPLC with fluorimetric detection using a newly designed and synthesized fluorescence derivatization reagent, 2,5-dioxopyrrolidin-1-yl (4-{[(2-nitrophenyl)sulfonyl]oxy}-6-(3-oxomorpholino)quinoline-2-carbonyl)prolinate [Ns-MOK-(R)- or (S)-Pro-OSu]. During the derivatization of VB with Ns-MOK-(R)-Pro-OSu at 60°C, the nosyl (Ns) group, which was introduced to protect a phenolic hydroxy group, was released within 30 min to produce MOK-(R)-Pro-VB, which was detected fluorimetrically at 448 nm with an excitation wavelength of 333 nm. The VB enantiomers were separated on an octadecylsilica (ODS) column with a resolution value of 5.57, because Ns-MOK-(R)-Pro-OSu bears an optically active D-proline structure. A complete separation of MOK-(R)-Pro-(R)- and -(S)-VB enantiomers was achieved on the ODS column within 40 min using stepwise gradient elution, and the detection limits were ~0.80 and 0.37 pmol on the column, respectively. The proposed HPLC with fluorimetric detection method was successfully used for determining VB enantiomers in VB-spiked human serum following solid-phase extraction with an anion-exchange cartridge.


Assuntos
Anticonvulsivantes/sangue , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia de Fase Reversa/métodos , Vigabatrina/sangue , Corantes Fluorescentes/química , Humanos , Indicadores e Reagentes/química
18.
Epilepsy Behav ; 113: 107531, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33248400

RESUMO

Epileptic Spasms (ES) is a type of seizure usually occurring in the context of a severe childhood epileptic syndrome associated to significant Electroencephalogram (EEG) abnormalities. There are three scenarios in which ES may occur. The first one is represented by West Syndrome (WS): ES occur in a previously non encephalopathic infant in association with the development of a hypsarrhythmic EEG pattern. In most cases, standard treatment with Adrenocorticotropic Hormone (ACTH), steroids or vigabatrin leads to a reversal of the electroclinical picture. The second scenario is represented by Developmental and Epileptic Encephalopathies (DEEs): ES are documented, often along other seizures types, in an infant who often shows developmental delay since birth; the EEG pattern is pathological both in wakefulness and in sleep, without typical features of hypsarrhythmia; therapies (with the exception of few potentially treatable syndromes) are poorly effective. The last scenario is represented by ES in the context of Focal Epilepsies (FEs): ES, sometimes showing focal signs or closely related to focal seizures, are associated with focal brain lesions. Treatment with ACTH, steroids or vigabatrin may not be effective as well as antiepileptic drugs for focal epilepsies. In drug-resistant patients, surgery should be considered. Although there are some gaps in our current scientific knowledge concerning the peculiar electroclinical and physiopathological features of ES, we nowadays possess the necessary tools to correctly frame this unique seizure type into one of these scenarios and therefore properly manage the diagnostic and therapeutic workup.


Assuntos
Epilepsia , Espasmos Infantis , Criança , Eletroencefalografia , Epilepsia/complicações , Epilepsia/tratamento farmacológico , Humanos , Lactente , Espasmo , Espasmos Infantis/tratamento farmacológico , Vigabatrina/uso terapêutico
19.
Expert Rev Neurother ; 20(12): 1315-1324, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33078964

RESUMO

Objective: Although vigabatrin (VGB) is effective and well tolerated for the treatment of epileptic spasms, there are safety concerns. The aim of this systematic review and metaanalysis was to assess adverse events of VGB for the treatment of epileptic spasms. Methods: MEDLINE, EMBASE, and Cochrane databases were searched. The population was infants treated with VGB for epileptic spasms. The outcomes were VGB-related adverse events. Meta-analyses of VGB-related MRI abnormalities, retinal toxicity as measured by electroretinogram (ERG), visual field defect as measured by perimetry, and other adverse events were conducted. Results: Fifty-seven articles were included in the systematic review. The rate of VGB-related MRI abnormalities was 21% (95% CI: 15-29%). Risk factors for MRI abnormalities were age younger than 12 months and higher VGB dose. VGB-related retinal toxicity and visual field defect occurred in 29% (95% CI: 7-69%) and 28% (95% CI: 4-78%) respectively. Other adverse events occurred in 23% (95% CI: 16-34%), consisting predominantly of central nervous system symptoms, and the majority of these did not require therapeutic modification. Conclusion: This study will inform physicians and families on the risk profile of VGB for the treatment of epileptic spasms and will help decisions on treatment options.


Assuntos
Anticonvulsivantes/efeitos adversos , Espasmos Infantis/tratamento farmacológico , Vigabatrina/efeitos adversos , Humanos , Lactente
20.
Epilepsia ; 61(10): e159-e164, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32944947

RESUMO

Vigabatrin (VGB), adrenocorticotropic hormone (ACTH), and prednisone are first-line treatments for infantile spasms (IS). A recent study reported benefits from the use of combination VGB and hormonal therapy over hormonal treatment alone in IS. We describe three patients with IS who developed acute encephalopathy with extrapyramidal symptoms, vigabatrin-associated brain abnormalities on magnetic resonance imaging (VABAM), and death in one patient shortly after initiation of therapy with VGB and ACTH. A literature review supports increased risk of fulminant, symptomatic VABAM in patients receiving VGB in association with hormonal therapy, raising concerns regarding its safety in IS.


Assuntos
Hormônio Adrenocorticotrópico/administração & dosagem , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/toxicidade , Espasmos Infantis/tratamento farmacológico , Vigabatrina/administração & dosagem , Vigabatrina/toxicidade , Encefalopatias/induzido quimicamente , Encefalopatias/diagnóstico por imagem , Quimioterapia Combinada , Evolução Fatal , Feminino , Humanos , Lactente , Masculino , Espasmos Infantis/diagnóstico por imagem
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