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1.
Mymensingh Med J ; 28(3): 712-715, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31391451

RESUMO

The prevalence of seizures in individuals with Down Syndrome (DS) is higher than in the general population. Rates of epilepsy in DS range from 1-13%. Forty percent of individuals develop seizures before 1 year of age and another 40% develop in their thirties or later. Boys have an earlier age of onset. The prevalence of epilepsy increases with age. Types of seizures are: 47% partial seizures, 32% infantile spasms and 21% generalized tonic-clonic seizures. Sex distribution for epilepsy in children with DS varies. Males have a younger age at onset. Trisomy 21 is common among epileptic children with DS but mosaicism or translocation has also been documented. The mechanisms underlying the increased seizure susceptibility in DS have not yet been completely explained. Seizures in infancy may be due to inherent structural brain abnormalities, like fewer inhibitory neurons, abnormal cortical lamination, persistent fetal dendritic morphology, underdeveloped synaptic profiles. Concentrations of carbonic anhydrase II are increased in the brains of young children with DS. It potentially increases seizure susceptibility. The pharmacological treatment of epilepsy in DS is same as that of other patients diagnosed with epilepsy. Individuals with DS have an unusually high number of side-effects from phenytoin. The diagnosis, classification and treatment of epilepsy in DS follow the guidelines applied to the general population. Review of literatures from 1960 to 2017 and electronically identified articles on epilepsy in Down syndrome in children in English are searched from internet and pub med to describe features of seizures in children with DS.


Assuntos
Anticonvulsivantes , Síndrome de Down , Epilepsias Parciais , Epilepsia Generalizada , Anticonvulsivantes/uso terapêutico , Carbamazepina , Criança , Pré-Escolar , Síndrome de Down/complicações , Epilepsias Parciais/tratamento farmacológico , Epilepsias Parciais/etiologia , Epilepsia Generalizada/tratamento farmacológico , Epilepsia Generalizada/etiologia , Humanos , Convulsões
2.
World Neurosurg ; 131: 58-61, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31376555

RESUMO

BACKGROUND: Postoperative blindness is a devastating surgical complication. Although usually associated with prolonged cardiac and prone spinal operations, it may follow other procedures as well. Postoperative blindness is most commonly caused by a vascular etiology, but it can more rarely be caused by status epilepticus. We have previously reported a case of this phenomenon following a staged spinal deformity surgery. CASE DESCRIPTION: Here we report 2 additional cases following a skull base procedure and a single stage lumbar spine surgery. In all instances, rapid recognition that the patients' blindness was due to occipital seizures resulted in acute antiepileptiform treatment and full restoration of vision. CONCLUSIONS: Although a rare phenomenon, this syndrome, first recognized and described by Tarik F. Ibrahim, should be considered in any patient with postoperative visual impairment.


Assuntos
Anticonvulsivantes/uso terapêutico , Cegueira/etiologia , Neoplasias Encefálicas/cirurgia , Epilepsias Parciais/tratamento farmacológico , Vértebras Lombares/cirurgia , Lobo Occipital , Complicações Pós-Operatórias/tratamento farmacológico , Estenose Espinal/cirurgia , Estado Epiléptico/tratamento farmacológico , Idoso , Neoplasias Encefálicas/secundário , Eletroencefalografia , Epilepsias Parciais/complicações , Feminino , Humanos , Levetiracetam , Base do Crânio , Estado Epiléptico/complicações
3.
Saudi Med J ; 40(7): 721-726, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31287134

RESUMO

Parry-Romberg syndrome is a rare disorder with progressive hemifacial atrophy of unknown etiology. We reported 2 cases of progressive hemifacial atrophy with different neurological manifestations from Kuwait. The first case was a 14-year-old boy who initially presented with recurrent transient stroke-like episodes followed by focal seizures and hemifacial atrophy. Magnetic resonance imaging showed significant white matter changes and cerebral hemiatrophy. The second case was a 7-year-old girl who presented with complex partial seizures and hemifacial atrophy, her magnetic resonance imaging scan showed minimal changes in the hemiatrophy of the temporal cerebral lobe. Both patients' disease activity was well controlled with immunosuppressive therapy and anticonvulsants. Parry-Romberg syndrome should be considered in any child with unexplained neurological symptoms.


Assuntos
Cérebro/diagnóstico por imagem , Epilepsias Parciais/fisiopatologia , Hemiatrofia Facial/fisiopatologia , Ataque Isquêmico Transitório/fisiopatologia , Adolescente , Anticonvulsivantes/uso terapêutico , Atrofia , Cérebro/patologia , Criança , Eletroencefalografia , Epilepsias Parciais/tratamento farmacológico , Epilepsias Parciais/etiologia , Hemiatrofia Facial/complicações , Hemiatrofia Facial/diagnóstico por imagem , Hemiatrofia Facial/tratamento farmacológico , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Ataque Isquêmico Transitório/etiologia , Kuweit , Imagem por Ressonância Magnética , Masculino , Metotrexato/uso terapêutico , Prednisolona/uso terapêutico
4.
Cochrane Database Syst Rev ; 7: CD005612, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31287157

RESUMO

BACKGROUND: Epilepsy is a common neurological disease that affects approximately 1% of the UK population. Approximately one-third of these people continue to have seizures despite drug treatment. Pregabalin is one of the newer antiepileptic drugs which have been developed to improve outcomes.This is an updated version of the Cochrane Review published in Issue 3, 2014, and includes three new studies. OBJECTIVES: To assess the efficacy and tolerability of pregabalin when used as an add-on treatment for drug-resistant focal epilepsy. SEARCH METHODS: For the latest update we searched the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), on 5 July 2018, MEDLINE (Ovid, 1946 to 5 July 2018), ClinicalTrials.gov (5 July 2018), and the World Health Organization International Clinical Trials Registry Platform (ICTRP, 5 July 2018), and contacted Pfizer Ltd, manufacturer of pregabalin, to identify published, unpublished, and ongoing trials. SELECTION CRITERIA: We included randomised controlled trials comparing pregabalin with placebo or an alternative antiepileptic drug as an add-on for people of any age with drug-resistant focal epilepsy. Double-blind and single-blind trials were eligible for inclusion. The primary outcome was 50% or greater reduction in seizure frequency; secondary outcomes were seizure freedom, treatment withdrawal for any reason, treatment withdrawal due to adverse effects, and proportion of individuals experiencing adverse effects. DATA COLLECTION AND ANALYSIS: Two review authors independently selected and assessed trials for eligibility and extracted data. Analyses were by intention-to-treat. We presented results as risk ratios (RR) and odds ratios (OR) with 95% confidence intervals (CIs). Two review authors assessed the included studies for risk of bias using the Cochrane 'Risk of bias' tool. MAIN RESULTS: We included nine industry-sponsored randomised controlled trials (3327 participants) in the review. Seven trials compared pregabalin to placebo. For the primary outcome, participants randomised to pregabalin were significantly more likely to attain a 50% or greater reduction in seizure frequency compared to placebo (RR 2.28, 95% CI 1.52 to 3.42, 7 trials, 2193 participants, low-certainty evidence). The odds of response doubled with an increase in dose from 300 mg/day to 600 mg/day (OR 1.99, 95% CI 1.74 to 2.28), indicating a dose-response relationship. Pregabalin was significantly associated with seizure freedom (RR 3.94, 95% CI 1.50 to 10.37, 4 trials, 1125 participants, moderate-certainty evidence). Participants were significantly more likely to withdraw from pregabalin treatment than placebo for any reason (RR 1.35, 95% CI 1.11 to 1.65, 7 trials, 2193 participants, moderate-certainty evidence) and for adverse effects (RR 2.65, 95% CI 1.88 to 3.74, 7 trials, 2193 participants, moderate-certainty evidence).Three trials compared pregabalin to three active-control drugs: lamotrigine, levetiracetam, and gabapentin. Participants allocated to pregabalin were significantly more likely to achieve a 50% or greater reduction in seizure frequency than those allocated to lamotrigine (RR 1.47, 95% CI 1.03 to 2.12, 1 trial, 293 participants) but not those allocated to levetiracetam (RR 0.94, 95% CI 0.80 to 1.11, 1 trial, 509 participants) or gabapentin (RR 0.96, 95% CI 0.82 to 1.12, 1 trial, 484 participants). We found no significant differences between pregabalin and lamotrigine (RR 1.39, 95% CI 0.40 to 4.83) for seizure freedom, however, significantly fewer participants achieved seizure freedom with add-on pregabalin compared to levetiracetam (RR 0.50, 95% CI 0.30 to 0.85). No data were reported for this outcome for pregabalin versus gabapentin. We found no significant differences between pregabalin and lamotrigine (RR 1.07, 95% CI 0.75 to 1.52), levetiracetam (RR 1.03, 95% CI 0.71 to 1.49), or gabapentin (RR 0.78, 95% CI 0.57 to 1.07) for treatment withdrawal due to any reason or due to adverse effects (pregabalin versus lamotrigine: RR 0.89, 95% CI 0.53 to 1.48; versus levetiracetam: RR 1.29, 95% CI 0.66 to 2.54; versus gabapentin: RR 1.07, 95% CI 0.54 to 2.11). Ataxia, dizziness, somnolence, weight gain, and fatigue were significantly associated with pregabalin.We rated the overall risk of bias in the included studies as low or unclear due to the possibility of publication bias and lack of methodological details provided. We rated the certainty of the evidence as very low to moderate using the GRADE approach. AUTHORS' CONCLUSIONS: Pregabalin, when used as an add-on drug for treatment-resistant focal epilepsy, is significantly more effective than placebo at producing a 50% or greater seizure reduction and seizure freedom. Results demonstrated efficacy for doses from 150 mg/day to 600 mg/day, with increasing effectiveness at 600 mg doses, however issues with tolerability were noted at higher doses. The trials included in this review were of short duration, and longer-term trials are needed to inform clinical decision making.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsias Parciais/tratamento farmacológico , Pregabalina/uso terapêutico , Quimioterapia Combinada , Gabapentina , Humanos , Lamotrigina , Levetiracetam , Ensaios Clínicos Controlados Aleatórios como Assunto , Convulsões/tratamento farmacológico
5.
Neurology ; 93(3): e227-e236, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31217259

RESUMO

OBJECTIVE: To obtain medical records, family interviews, and death-related reports of sudden unexpected death in epilepsy (SUDEP) cases to better understand SUDEP. METHODS: All cases referred to the North American SUDEP Registry (NASR) between October 2011 and June 2018 were reviewed; cause of death was determined by consensus review. Available medical records, death scene investigation reports, autopsy reports, and next-of-kin interviews were reviewed for all cases of SUDEP. Seizure type, EEG, MRI, and SUDEP classification were adjudicated by 2 epileptologists. RESULTS: There were 237 definite and probable cases of SUDEP among 530 NASR participants. SUDEP decedents had a median age of 26 (range 1-70) years at death, and 38% were female. In 143 with sufficient information, 40% had generalized and 60% had focal epilepsy. SUDEP affected the full spectrum of epilepsies, from benign epilepsy with centrotemporal spikes (n = 3, 1%) to intractable epileptic encephalopathies (n = 27, 11%). Most (93%) SUDEPs were unwitnessed; 70% occurred during apparent sleep; and 69% of patients were prone. Only 37% of cases of SUDEP took their last dose of antiseizure medications (ASMs). Reported lifetime generalized tonic-clonic seizures (GTCS) were <10 in 33% and 0 in 4%. CONCLUSIONS: NASR participants commonly have clinical features that have been previously been associated with SUDEP risk such as young adult age, ASM nonadherence, and frequent GTCS. However, a sizeable minority of SUDEP occurred in patients thought to be treatment responsive or to have benign epilepsies. These results emphasize the importance of SUDEP education across the spectrum of epilepsy severities. We aim to make NASR data and biospecimens available for researchers to advance SUDEP understanding and prevention.


Assuntos
Epilepsias Parciais/epidemiologia , Epilepsia Generalizada/epidemiologia , Adesão à Medicação/estatística & dados numéricos , Decúbito Ventral , Sono , /epidemiologia , Adolescente , Adulto , Idoso , Anticonvulsivantes/uso terapêutico , Criança , Pré-Escolar , Epilepsias Parciais/tratamento farmacológico , Epilepsia Generalizada/tratamento farmacológico , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , América do Norte , Sistema de Registros , Fatores de Risco , Convulsões/epidemiologia , Adulto Jovem
6.
Cochrane Database Syst Rev ; 6: CD010541, 2019 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-31237346

RESUMO

BACKGROUND: This is an updated version of the original Cochrane review, published in 2015.Focal epilepsies are caused by a malfunction of nerve cells localised in one part of one cerebral hemisphere. In studies, estimates of the number of individuals with focal epilepsy who do not become seizure-free despite optimal drug therapy vary between at least 20% and up to 70%. If the epileptogenic zone can be located, surgical resection offers the chance of a cure with a corresponding increase in quality of life. OBJECTIVES: The primary objective is to assess the overall outcome of epilepsy surgery according to evidence from randomised controlled trials.Secondary objectives are to assess the overall outcome of epilepsy surgery according to non-randomised evidence, and to identify the factors that correlate with remission of seizures postoperatively. SEARCH METHODS: For the latest update, we searched the following databases on 11 March 2019: Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1946 to March 08, 2019), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA: Eligible studies were randomised controlled trials (RCTs) that included at least 30 participants in a well-defined population (age, sex, seizure type/frequency, duration of epilepsy, aetiology, magnetic resonance imaging (MRI) diagnosis, surgical findings), with an MRI performed in at least 90% of cases and an expected duration of follow-up of at least one year, and reporting an outcome related to postoperative seizure control. Cohort studies or case series were included in the previous version of this review. DATA COLLECTION AND ANALYSIS: Three groups of two review authors independently screened all references for eligibility, assessed study quality and risk of bias, and extracted data. Outcomes were proportions of participants achieving a good outcome according to the presence or absence of each prognostic factor of interest. We intended to combine data with risk ratios (RRs) and 95% confidence intervals (95% CIs). MAIN RESULTS: We identified 182 studies with a total of 16,855 included participants investigating outcomes of surgery for epilepsy. Nine studies were RCTs (including two that randomised participants to surgery or medical treatment (99 participants included in the two trials received medical treatment)). Risk of bias in these RCTs was unclear or high. Most of the remaining 173 non-randomised studies followed a retrospective design. We assessed study quality using the Effective Public Health Practice Project (EPHPP) tool and determined that most studies provided moderate or weak evidence. For 29 studies reporting multivariate analyses, we used the Quality in Prognostic Studies (QUIPS) tool and determined that very few studies were at low risk of bias across domains.In terms of freedom from seizures, two RCTs found surgery (n = 97) to be superior to medical treatment (n = 99); four found no statistically significant differences between anterior temporal lobectomy (ATL) with or without corpus callosotomy (n = 60), between subtemporal or transsylvian approach to selective amygdalohippocampectomy (SAH) (n = 47); between ATL, SAH and parahippocampectomy (n = 43) or between 2.5 cm and 3.5 cm ATL resection (n = 207). One RCT found total hippocampectomy to be superior to partial hippocampectomy (n = 70) and one found ATL to be superior to stereotactic radiosurgery (n = 58); and another provided data to show that for Lennox-Gastaut syndrome, no significant differences in seizure outcomes were evident between those treated with resection of the epileptogenic zone and those treated with resection of the epileptogenic zone plus corpus callosotomy (n = 43). We judged evidence from the nine RCTs to be of moderate to very low quality due to lack of information reported about the randomised trial design and the restricted study populations.Of the 16,756 participants included in this review who underwent a surgical procedure, 10,696 (64%) achieved a good outcome from surgery; this ranged across studies from 13.5% to 92.5%. Overall, we found the quality of data in relation to recording of adverse events to be very poor.In total, 120 studies examined between one and eight prognostic factors in univariate analysis. We found the following prognostic factors to be associated with a better post-surgical seizure outcome: abnormal pre-operative MRI, no use of intracranial monitoring, complete surgical resection, presence of mesial temporal sclerosis, concordance of pre-operative MRI and electroencephalography, history of febrile seizures, absence of focal cortical dysplasia/malformation of cortical development, presence of tumour, right-sided resection, and presence of unilateral interictal spikes. We found no evidence that history of head injury, presence of encephalomalacia, presence of vascular malformation, and presence of postoperative discharges were prognostic factors of outcome.Twenty-nine studies reported multi-variable models of prognostic factors, and showed that the direction of association of factors with outcomes was generally the same as that found in univariate analyses.We observed variability in many of our analyses, likely due to small study sizes with unbalanced group sizes and variation in the definition of seizure outcome, the definition of prognostic factors, and the influence of the site of surgery AUTHORS' CONCLUSIONS: Study design issues and limited information presented in the included studies mean that our results provide limited evidence to aid patient selection for surgery and prediction of likely surgical outcomes. Future research should be of high quality, follow a prospective design, be appropriately powered, and focus on specific issues related to diagnostic tools, the site-specific surgical approach, and other issues such as extent of resection. Researchers should investigate prognostic factors related to the outcome of surgery via multi-variable statistical regression modelling, where variables are selected for modelling according to clinical relevance, and all numerical results of the prognostic models are fully reported. Journal editors should not accept papers for which study authors did not record adverse events from a medical intervention. Researchers have achieved improvements in cancer care over the past three to four decades by answering well-defined questions through the conduct of focused RCTs in a step-wise fashion. The same approach to surgery for epilepsy is required.


Assuntos
Epilepsias Parciais/cirurgia , Adolescente , Adulto , Análise de Variância , Anticonvulsivantes/uso terapêutico , Criança , Epilepsias Parciais/tratamento farmacológico , Feminino , Hipocampo/cirurgia , Humanos , Masculino , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Resultado do Tratamento
7.
Eur J Paediatr Neurol ; 23(4): 589-603, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31171490

RESUMO

Extrapolation of efficacy data from adults to children is accepted for focal epilepsy - the antiepileptic drug, lacosamide, has been approved for the treatment of children ≥4 years of age on this basis. Since many small-scale, open-label studies are reported in the literature before approval, a systematic review was conducted to ascertain whether results of these could be used to support extrapolation in epilepsy in the future. In the absence of randomised trials, a second analysis was conducted for reports on lacosamide use in adults with generalized epilepsies. Twenty-seven articles were included in the paediatric qualitative synthesis, and 14 in the adult. Paediatric studies were analysed separately based on seizure type: focal, generalised and mixed. In focal epilepsy, safety and seizure-related findings mirrored those observed in the adult Phase II/III trials, supporting the feasibility of data extrapolation. Few studies reported outcomes in children with epilepsies associated with generalised seizures, and those that included children with different seizure types, mostly did not provide results separately. Lacosamide treatment appeared beneficial for children and adults experiencing tonic-clonic and myoclonic seizures. Reports of seizure aggravation were inconsistent and, in many cases, could not be clearly attributed to lacosamide. Given the absence of sufficient data, evidence for the feasibility of extrapolation was not as clear-cut as it was in focal epilepsy. These results highlight the complexities of conducting trials in the generalised epilepsy setting, and the importance of studies in the real-life setting and of analysing efficacy data per generalized seizure type and syndrome.


Assuntos
Fatores Etários , Anticonvulsivantes/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Lacosamida/uso terapêutico , Estudos Observacionais como Assunto , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino
8.
Cochrane Database Syst Rev ; 6: CD012065, 2019 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-31233229

RESUMO

BACKGROUND: This is an updated version of the original Cochrane Review published in Issue 12, 2016. This review is one in a series of Cochrane Reviews investigating pair-wise monotherapy comparisons.Epilepsy is a common neurological condition in which abnormal electrical discharges from the brain cause recurrent unprovoked seizures. It is believed that with effective drug treatment, up to 70% of individuals with active epilepsy have the potential to become seizure-free and go into long-term remission shortly after starting drug therapy, the majority of which may be able to achieve remission with a single antiepileptic drug (AED).The correct choice of first-line AED for individuals with newly diagnosed seizures is of great importance and should be based on the highest-quality evidence available regarding the potential benefits and harms of various treatments for an individual.Topiramate and carbamazepine are commonly used AEDs. Performing a synthesis of the evidence from existing trials will increase the precision of results of outcomes relating to efficacy and tolerability, and may help inform a choice between the two drugs. OBJECTIVES: To review the time to treatment failure, remission and first seizure with topiramate compared with carbamazepine when used as monotherapy in people with focal onset seizures (simple or complex focal and secondarily generalised), or generalised onset tonic-clonic seizures (with or without other generalised seizure types). SEARCH METHODS: For the latest update we searched the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (Ovid); ClinicalTrials.gov; and the WHO International Clinical Trials Registry Platform (ICTRP) to 22 May 2018. We imposed no language restrictions. We also contacted pharmaceutical companies and trial investigators. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing monotherapy with either topiramate or carbamazepine in children or adults with focal onset seizures or generalised onset tonic-clonic seizures (with or without other generalised seizure types). DATA COLLECTION AND ANALYSIS: This was an individual participant data (IPD), review. Our primary outcome was time to treatment failure. Our secondary outcomes were time to first seizure post-randomisation, time to six-month remission, time to 12-month remission, and incidence of adverse events. We used Cox proportional hazards regression models to obtain trial-specific estimates of hazard ratios (HRs), with 95% confidence intervals (CIs), using the generic inverse variance method to obtain the overall pooled HR and 95% CI. MAIN RESULTS: IPD were available for 1151 of 1239 eligible individuals from two of three eligible studies (93% of the potential data). A small proportion of individuals recruited into these trials had 'unclassified seizures;' for analysis purposes, these individuals are grouped with those with generalised onset seizures. For remission outcomes, a HR < 1 indicated an advantage for carbamazepine, and for first seizure and treatment failure outcomes, a HR < 1 indicated an advantage for topiramate.The main overall results for the primary outcome, time to treatment failure, given as pooled HR adjusted for seizure type were: time to failure for any reason related to treatment 1.16 (95% CI 0.97 to 1.38); time to failure due to adverse events 1.02 (95% CI 0.82 to 1.27); and time to failure due to lack of efficacy 1.46 (95% CI 1.08 to 1.98). Overall results for secondary outcomes were time to first seizure 1.11 (95% CI 0.96 to 1.29); and time to six-month remission 0.88 (0.76 to 1.01). There were no statistically significant differences between the drugs. A statistically significant advantage for carbamazepine was shown for time to 12-month remission: 0.84 (95% CI 0.71 to 0.99).The results of this review are applicable mainly to individuals with focal onset seizures; 81% of individuals included within the analysis experienced seizures of this type at baseline. For individuals with focal onset seizures, a statistically significant advantage for carbamazepine was shown for time to failure for any reason related to treatment (HR 1.21, 95% CI 1.01 to 1.46), time to treatment failure due to lack of efficacy (HR 1.47, 95% CI 1.07 to 2.02), and time to 12-month remission (HR 0.82, 95% CI 0.69 to 0.99). There was no statistically significant difference between topiramate and carbamazepine for 'time to first seizure' and 'time to six-month remission'.Evidence for individuals with generalised tonic-clonic seizures (9% of participants contributing to the analysis), and unclassified seizure types (10% of participants contributing to the analysis) was very limited; no statistically significant differences were found but CIs were wide; therefore we cannot exclude an advantage to either drug, or a difference between drugs.The most commonly reported adverse events with both drugs were drowsiness or fatigue, "pins and needles" (tingling sensation), headache, gastrointestinal disturbance and anxiety or depression. The rate of adverse events was similar across the two drugs.We judged the methodological quality of the included trials generally to be good; however, there was some evidence that the open-label design of the larger of the two trials may have influenced the treatment failure rate within the trial. Hence, we judged the certainty of the evidence for treatment failure to be moderate for individuals with focal onset seizures and low for individuals with generalised onset seizures. For efficacy outcomes (first seizure, remission), we judged the certainty of evidence from this review to be high for individuals with focal onset seizures and moderate for individuals with generalised onset or unclassified seizures. AUTHORS' CONCLUSIONS: For individuals with focal onset seizures, there is moderate-certainty evidence that carbamazepine is less likely to be withdrawn and high-certainty evidence that 12-month remission will be achieved earlier than with topiramate. We did not find any differences between the drugs in terms of the other outcomes measured in the review and for individuals with generalised tonic-clonic seizures or unclassified epilepsy; however, we encourage caution in the interpretation of results including small numbers of participants with these seizure types.Future trials should be designed to the highest quality possible and take into consideration masking, choice of population, classification of seizure type, duration of follow-up, choice of outcomes and analysis, and presentation of results.


Assuntos
Anticonvulsivantes/uso terapêutico , Carbamazepina/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Epilepsia Tônico-Clônica/tratamento farmacológico , Topiramato/uso terapêutico , Adolescente , Adulto , Anticonvulsivantes/efeitos adversos , Carbamazepina/efeitos adversos , Criança , Pré-Escolar , Epilepsia Generalizada/tratamento farmacológico , Feminino , Humanos , Quimioterapia de Indução , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Fatores de Tempo , Topiramato/efeitos adversos , Falha de Tratamento
9.
Seizure ; 69: 235-240, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31121547

RESUMO

PURPOSE: Interictal epileptiform discharges (IEDs) have high diagnostic value concerning patients with epilepsy and the instances of obtaining IEDs increase with longer recording times. However, the merit of a single, extended electroencephalography (EEG) recording in detecting IEDs has not been substantiated. We aimed to determine the optimal duration of an EEG required to diagnose epilepsy in different seizure types. METHODS: Overall, 84 patients-29 with generalised onset epilepsy and 55 with focal onset epilepsy-were evaluated. Long-term video electroencephalographic monitoring (VEM) was analysed to find the first definite IED besides assessing the first seizure and latency. RESULTS: The median latency of the first IED (12 min, ranging from 1 to 440 min vs. 55 min, ranging from 2 to 7500 min; p = 0.014) and the median duration of a VEM recording (2 d, ranging from 1 to 10 d vs. 3 d, ranging from 1 to 10 d; p = 0.012) were found significantly lower in the generalised epilepsy group compared with that in the focal epilepsy group. CONCLUSIONS: Generalised onset epilepsy showed a significantly shorter latency to IED and VEM duration compared with focal onset epilepsy. In our data set, all the patients with generalised onset epilepsy had interictal IED within 10 h, but the patients with focal onset epilepsy required monitoring for three days to obtain IED.


Assuntos
Encéfalo/fisiopatologia , Eletroencefalografia , Epilepsias Parciais/fisiopatologia , Epilepsia Generalizada/fisiopatologia , Convulsões/fisiopatologia , Adolescente , Adulto , Anticonvulsivantes/uso terapêutico , Encéfalo/efeitos dos fármacos , Criança , Epilepsias Parciais/tratamento farmacológico , Epilepsia Generalizada/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Convulsões/tratamento farmacológico , Fatores de Tempo , Gravação em Vídeo , Adulto Jovem
10.
Epilepsy Res ; 153: 40-48, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30965274

RESUMO

OBJECTIVE: To assess the efficacy and safety of levetiracetam (LEV) as adjunctive treatment in children (0-18 years) with focal-onset seizures (FOS) with a larger dataset. METHODS: A pooled analysis would be performed for prospective clinical trials and a meta-analysis for controlled studies. Retrospectives studies were also summarized using descriptive statistics. RESULTS: Thirty-one articles (1763 patients) were identified, eighteen prospective self-controlled studies and thirteen retrospective studies. LEV was more effective than placebo, the pooled risk ratios (RRs) and 95% confidence intervals (CIs) for the 50% responder rate, seizure freedom rate and the median percentage reduction rate were 1.98 (1.49-2.63), 5.12 (2.09-12.51) and 3.19 (2.37-4.30), respectively. The overall response rates (ORRs) and 95% CIs were 56% (52%-60%), 14% (9%-19%) and 55% (31%-79%), respectively. For safety assessment, the pooled RRs and 95% CIs for the at least one treatment-emergent adverse events (TEAE) rate and at least one adverse drug reactions related (ADR-related) TEAE rate were 1.03 (0.94-1.13) and 1.45 (1.13-1.86) between two group. The ORRs and 95% CIs were 74% (54%-94%) and 48% (40%-55%). The adverse events significantly associated with LEV were somnolence 2.26 (95% CI 1.30-3.93) and hostility 2.33 (95% CI 1.15-4.70). The most frequency adverse events were pyrexia, headache, nervousness, upper respiratory tract and somnolence. The RRs for withdrawal rate or the ADR-related withdrawal rate were 0.77 (95% CI 0.44-1.38) and 0.91 (0.42-1.98), the ORRs were 17% (5%-28%) and 6% (4%-8%). CONCLUSION: The meta-analysis suggested that add-on LEV can significantly reduce seizure frequency and fairly tolerated compared to placebo.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Levetiracetam/uso terapêutico , Criança , Humanos
12.
Expert Opin Pharmacother ; 20(8): 909-915, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30908087

RESUMO

INTRODUCTION: About 70 million people worldwide are estimated to suffer from epilepsy. Despite a large variety of old and new antiepileptic drugs on the market, about 30% of people with epilepsy do not become seizure-free with medical treatment. This is a major individual and public health burden. Most of these difficult-to-treat patients are having focal seizures. Zonisamide is effective against focal seizures in adults and children and, thus, a therapeutic option for such patients. Its safety profile needs special attention. Areas covered: Herein, the authors discuss the pharmacology, clinical efficacy and the adverse effects of zonisamide. The article is derived from clinical trial data, long-term studies, meta-analyses, review articles, text books, webpages, and official license information. Expert opinion: Zonisamide has proven to be efficacious in focal epilepsy in children and adults, although it is not more effective than carbamazepine or other antiepileptic drugs. It is also effective in generalized epilepsy and in several other conditions of the CNS. Its safety profile may prevent it from becoming a first-line drug for focal epilepsy or any other indication.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Zonisamida/uso terapêutico , Adulto , Carbamazepina/uso terapêutico , Criança , Epilepsia Generalizada/tratamento farmacológico , Humanos , Convulsões/tratamento farmacológico , Resultado do Tratamento
13.
Acta Neurol Belg ; 119(2): 155-162, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30868468

RESUMO

Epilepsy is a neurologic disorder consisting of recurrent spontaneous seizures. Antiepileptic drugs administration is the most commonly used therapeutic strategy in the management of epilepsy. However, 20-30% of epilepsy patients have seizure episodes that are not controlled by these medicines (drug-resistant epilepsy). The management of drug-resistant epilepsy, especially in the children, is challenging and can cause economic and social problems, and lower the patients' quality of life, cognition, and mood. Several therapeutic approaches for drug-resistant epilepsy are available including surgical methods, neurostimulation treatments, and diet therapies which lead to diminishing the epileptic seizures. An increasing number of novel and potential therapeutic approaches such as gene therapy, gene editing, cell therapy, exosome therapy, and molecular network targeting have also been explored. The present study is aimed to review these current and emerging therapeutic approaches for drug-resistant epilepsy.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia/tratamento farmacológico , Convulsões/tratamento farmacológico , Epilepsias Parciais/tratamento farmacológico , Humanos , Qualidade de Vida
14.
Clin Neuropharmacol ; 42(3): 97-98, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30829883

RESUMO

Levetiracetam is an antiepileptic agent that is used for partial and generalized epilepsy. Although it is well tolerated in most cases, behavioral and nonbehavioral adverse effects may be observed. Among behavioral symptoms, depression, hostility, and agitation have been frequently reported. However, mania or mania-like symptoms are relatively rare, especially in children and adolescents. Hereby, we report mania-like symptoms with levetiracetam use in a 15-year-old boy. Mania-like symptoms emerged 3 weeks after starting levetiracetam and disappeared after adding risperidone to ongoing levetiracetam treatment.


Assuntos
Anticonvulsivantes/efeitos adversos , Transtorno Bipolar/induzido quimicamente , Epilepsias Parciais/tratamento farmacológico , Levetiracetam/efeitos adversos , Adolescente , Humanos , Masculino , Risperidona/uso terapêutico
15.
Epileptic Disord ; 21(1): 48-54, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30782581

RESUMO

Several recent studies have reported potassium sodium-activated channel subfamily T member 1 (KCNT1) mutations in epilepsy patients on quinidine therapy. The efficacy and safety of quinidine for epilepsy treatment, however, remains controversial. We herein report the cases of four patients with KCNT1 mutations treated with quinidine. A reduction in seizures of more than 50% after quinidine treatment was observed in one patient with epilepsy of infancy with migrating focal seizures (EIMFS), whereas two patients with EIMFS and one with focal epilepsy did not achieve apparent seizure reduction. The relationship between quinidine dose and serum quinidine concentration was inconsistent, particularly at high quinidine doses. One patient with EIMFS developed ventricular tachycardia the day after an increase in quinidine dose from 114 to 126 mg/kg/day. The serum trough quinidine concentration and the corrected QT interval (QTc) before arrhythmia onset were 2.4 µg/ml and 420 ms, respectively, and peak serum quinidine concentration after arrhythmia onset was 9.4 µg/ml. Another patient with EIMFS showed aberrant intraventricular conduction with a quinidine dose of 74.5 mg/kg/day and a serum trough concentration of 3.2 µg/ml. Given that serum quinidine levels may elevate sharply after a dose increase, careful monitoring of electrocardiographs and serum concentrations is required. Based on a review of previous reports and our experience with this case, quinidine should be considered as a promising drug for patients with EIMFS harbouring KCNT1 mutations, however, its efficacy remains controversial due to the limited number of cases, and more information on optimal serum concentrations and appropriate titration methods is required.


Assuntos
Anticonvulsivantes/farmacologia , Arritmias Cardíacas/induzido quimicamente , Epilepsias Parciais/tratamento farmacológico , Proteínas do Tecido Nervoso/genética , Canais de Potássio/genética , Quinidina/farmacologia , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/sangue , Criança , Pré-Escolar , Monitoramento de Medicamentos , Eletrocardiografia , Feminino , Humanos , Lactente , Masculino , Quinidina/administração & dosagem , Quinidina/efeitos adversos , Quinidina/sangue
16.
J Med Econ ; 22(4): 359-364, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30652931

RESUMO

BACKGROUND AND AIMS: Epilepsy is the most common serious neurological disorder worldwide. Approximately 40% of patients with focal epileptic seizures remain uncontrolled with antiepileptic drug (AED) monotherapy or polytherapy. Lacosamide has been recently approved by the European Medicines Agency as monotherapy for the treatment of focal seizures. The aim of this study was to estimate the cost-effectiveness of lacosamide compared with zonisamide as first-line treatment of focal epilepsy in patients with epilepsy aged ≥ 16 years to inform clinical decision-making in Greece. METHODS: A discrete event simulation model was adapted to reflect treatment pathways and resource use within the Greek national healthcare system, as specified by clinical experts. The model captures time-varying events and patient characteristics. Clinical inputs were sourced from pivotal trials and a network meta-analysis comparing lacosamide with other AEDs. The model predicts disease progression and seizures, relevant and most common adverse events, withdrawal due to lack of efficacy or adverse events, and epilepsy-specific and all-cause mortality over a 2-year time horizon. Unit costs were retrieved from published Greek sources. Health outcomes were measured as quality-adjusted life years (QALYs); secondary outcome was the cost per seizure avoided. Robustness of the results was tested with univariate and probabilistic sensitivity analyses. RESULTS: The lacosamide treatment pathway was associated with higher costs (i.e. €1,064) and an additional 0.119 QALYs when compared with zonisamide, resulting in an incremental cost-effectiveness ratio of €8,938 per QALY gained. The sensitivity analyses demonstrated that the results are most sensitive to the efficacy and utility estimates. LIMITATIONS: There are a number of limitations which stem from the process of model adaptation and lack of local real-world evidence. CONCLUSIONS: Lacosamide is a cost-effective option at a willingness-to-pay threshold of €30,000 per QALY, representing a valuable monotherapy treatment option for patients with focal epileptic seizures in the Greek setting.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Lacosamida/uso terapêutico , Zonisamida/uso terapêutico , Adulto , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/economia , Simulação por Computador , Análise Custo-Benefício , Progressão da Doença , Feminino , Grécia , Gastos em Saúde , Recursos em Saúde/economia , Recursos em Saúde/estatística & dados numéricos , Humanos , Lacosamida/efeitos adversos , Lacosamida/economia , Masculino , Pessoa de Meia-Idade , Anos de Vida Ajustados por Qualidade de Vida , Zonisamida/economia
17.
Acta Neurol Scand ; 139(1): 33-41, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30194755

RESUMO

Second and third generation AEDs have been directly compared to controlled-release carbamazepine (CBZ-CR) as initial monotherapy for new-onset focal epilepsy. Conversely, no head-to-head trials have been performed. The aim of this study was to estimate the comparative efficacy and tolerability of the antiepileptic monotherapies in adults with newly diagnosed focal epilepsy through a network meta-analysis (NMA). Randomized, double-blinded, parallel group, monotherapy studies comparing any AED to CBZ-CR in adults with newly diagnosed untreated epilepsy with focal-onset seizures was identified. The outcome measures were the seizure freedom for 6 and 12 months, the occurrence of treatment-emergent adverse events (TEAEs), and the treatment withdrawal due to TEAEs. Mixed treatment comparisons were conducted by a Bayesian NMA using the Markov chain Monte Carlo methods. Effect sizes were calculated as odds ratios (ORs) with 95% credible intervals (CrIs). Four trials were included involving 2856 participants, 1445 for CBZ-CR and 1411 for the comparative AEDs. Monotherapy AEDs compared to CBR-CR were levetiracetam (LEV), zonisamide (ZNS), lacosamide (LCM), and eslicarbazepine acetate (ESL). There were no statistical differences in the 6- and 12-month seizure freedom and TEAEs occurrence between LEV, ZNS, LCM, ESL, and CBZ-CR In the analysis of drug withdrawal due to TEAEs, LCM treatment was associated with a significantly lower discontinuation rate than CBZ-CR (OR 0.659, 95% CrI 0.428-0.950). LEV, ZNS, LCM, and ESL are effective initial monotherapy treatments in adult patients with newly diagnosed focal epilepsy and represent suitable alternatives to CBZ-CR.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Adulto , Humanos , Masculino , Meta-Análise em Rede , Resultado do Tratamento
18.
Brain Struct Funct ; 224(1): 9-18, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30238209

RESUMO

In the present study, we mapped the spatio-temporal dynamics of cortical responses to ipsilateral median nerve stimulation using intracerebral recordings (stereo-EEG) in 38 drug-resistant epileptic patients. Furthermore, we compared the pattern of responsiveness obtained in the same leads across ipsilateral and contralateral stimulations. Ipsilateral responses were found mostly confined to SII and posterior insula, while no activity was found in ipsilateral SI. By examining the temporal profiles of activation, ipsilateral SII showed a prominent tonic pattern, while contralateral SII exhibited both phasic and tonic responses. Beyond the localization of the active cortical nodes, these data contributed to identify the cortico-cortical connections carrying the somatosensory information to the ipsilateral hemisphere, with a major role of transcallosal projections from contralateral SII. In light of previous literature and of its localization, the functional role possibly covered by long lasting discharge in SII and insular cortex is also discussed. Overall, the presence of tonic activities was neglected so far due to the impossibility to identify deep sources along with a resolved description of their time course. The use of stereo-EEG, instead, allows one to achieve a four-dimensional characterization, complementing the classical view about the somatosensory system organization.


Assuntos
Epilepsias Parciais/fisiopatologia , Potenciais Somatossensoriais Evocados , Nervo Mediano/fisiopatologia , Córtex Somatossensorial/fisiopatologia , Adulto , Anticonvulsivantes/uso terapêutico , Mapeamento Encefálico/métodos , Resistência a Medicamentos , Estimulação Elétrica , Eletroencefalografia , Epilepsias Parciais/diagnóstico , Epilepsias Parciais/tratamento farmacológico , Epilepsias Parciais/psicologia , Feminino , Humanos , Masculino , Fatores de Tempo , Tato , Percepção do Tato , Adulto Jovem
19.
Seizure ; 64: 23-28, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30529755

RESUMO

PURPOSE: This study is to compare the efficacy of substitution with add-on therapy in patients with focal epilepsy, whose first monotherapy has failed after receiving usual treatments. METHODS: This is a prospective, long-term, non-randomized observational cohort study. Data were collected from Wenzhou Epilepsy Follow Up Registry Database. Focal epilepsy patients from January 2003 to June 2015, whose first monotherapy had failed, were registered. The total observation period was three years. The major outcome measure was seizure remission rate. The secondary outcome measures included retention rates and incidences of intolerable adverse events. RESULTS: A total of 596 patients were included, among them 209 received substitution therapy, and 387 received add-on therapy. Seizure remission rates were 56.5% by substitution therapy and 39.0% by add-on therapy, respectively (p = 0.025). Retention rate was 49.3% by substitution therapy, and 36.2% by add-on therapy (p = 0.031). Incidence of intolerable adverse events for substitution and add-on was 4.8% and 7.2%, respectively (p = 0.243). There were 457 patients who failed to the first monotherapy due to lack of efficacy. In these patients, seizure remission rates of substitution and add-on were 51.0% and 38.1%, respectively (p = 0.171). Retention rates were 48.1% and 36.0%, respectively (p = 0.136). And, incidences of intolerable adverse events were 2.9% and 6.8%, respectively (p = 0.137). CONCLUSION: The seizure remission rate and retention rate of substitution therapy are better than those of add-on therapy for focal epilepsy patients whose first monotherapy fails.


Assuntos
Anticonvulsivantes/administração & dosagem , Prescrições de Medicamentos/estatística & dados numéricos , Quimioterapia Combinada/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Epilepsias Parciais/tratamento farmacológico , Sistema de Registros/estatística & dados numéricos , Anticonvulsivantes/efeitos adversos , China/epidemiologia , Epilepsias Parciais/epidemiologia , Humanos , Estudos Prospectivos , Indução de Remissão
20.
Acta Neurol Scand ; 139(4): 360-368, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30506559

RESUMO

OBJECTIVES: Evaluate long-term effectiveness and tolerability of brivaracetam in clinical practice in patients with focal epilepsy. MATERIALS AND METHODS: This was a multicenter retrospective study. Patients aged ≥16 years were started on brivaracetam from November 2016 to June 2017 and followed over 1 year. Data were obtained from medical records at 3, 6 and 12 months after treatment initiation for evaluation of safety- and seizure-related outcomes. RESULTS: A total of 575 patients were included in analyses; most had been treated with ≥4 lifetime antiepileptic drugs. Target dosage was achieved by 30.6% of patients on the first day. Analysis of primary variables at 12 months revealed that mean reduction in seizure frequency was 36.0%, 39.7% of patients were ≥50% responders and 17.5% were seizure-free. Seizure-freedom was achieved by 37.5% of patients aged ≥65 years. Incidence of adverse events (AEs) and psychiatric AEs (PAEs) was 39.8% and 14.3%, respectively, and discontinuation due to these was 8.9% and 3.7%, respectively. Somnolence, irritability, and dizziness were the most frequently reported AEs. At baseline, 228 (39.7%) patients were being treated with levetiracetam; most switched to brivaracetam (dose ratio 1:10-15). Among those who switched because of PAEs (n = 53), 9 (17%) reported PAEs on brivaracetam, and 3 (5.7%) discontinued because of PAEs. Tolerability was not highly affected among patients with learning disability or psychiatric comorbidity. CONCLUSIONS: In a large population of patients with predominantly drug-resistant epilepsy, brivaracetam was effective and well-tolerated; no unexpected AEs occurred over 1 year, and the incidence of PAEs was lower compared with levetiracetam.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Pirrolidinonas/uso terapêutico , Adolescente , Adulto , Idoso , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Convulsões/prevenção & controle , Resultado do Tratamento , Adulto Jovem
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