[New antiepileptic drugs]. / Nuevos fármacos antiepilépticos.

Antiepileptic drugs are the first treatment option in patients with epilepsy. Drugs developed after 2000 are known as third generation antiepileptic drugs. These medications offer new mechanisms of action and favorable pharmacokinetics, decreasing the occurrence of side effects and drug-drug interactions. Broad spectrum antiepileptic drugs, such as brivaracetam and clobazam are good choices for generalized tonic colonic seizures and are well tolerated.New sodium channel blockers such as lacosamide and eslicarbazepine, have a more "benign" side effect profile than the first or second generation of sodium channel blockers. These new drugs are useful therapies in patients with epilepsy of difficult control. Cannabidiol and fenfluramine are useful in the treatment of Dravet or Lennox Gastaut syndrome. Allopregnenolona and ganaxolone showed good efficacy in status epilepticus and could play an important future role in this clinical scenario.

Los fármacos antiepilépticos constituyen el tratamiento inicial en pacientes con epilepsia. Los antIepilépticos producidos después del año 2000 se conocen como fármacos de tercera generación. Estas drogas ofrecen nuevos mecanismos de acción y una farmacocinética más favorable, minimizando efectos adversos o interacciones medicamentosas. Las drogas de amplio espectro como brivaracetam y clobazam son una buena opción en casos de crisis generalizadas y poseen un grado de tolerabilidad muy aceptable. Los nuevos antiepilépticos bloqueadores de canales de sodio, como lacosamida y eslicarbazepina tienen un perfil de efectos adversos más favorable que los bloqueadores de sodio de primera o segunda generación. Estos nuevos medicamentos pueden utilizarse en pacientes con epilepsia de difícil control. Cannabidiol y fenfluramina son muy útiles en el tratamiento del síndrome de Dravet o Lennox Gastaut. La Alopregnenolona y ganaxolona demuestran buena eficacia en casos de estado epiléptico y podrían en el futuro cercano tener un papel importante en este escenario clínico.

Nuevos fármacos antiepilépticos / New antiepileptic drugs

Los fármacos antiepilépticos constituyen el tratamiento inicial en pacientes con epilepsia. Los antIepilépticos producidos después del año 2000 se conocen como fármacos de tercera generación. Estas drogas ofrecen nuevos mecanismos de acción y una farmacocinética más favorable, minimizando efectos adversos o interacciones medicamentosas. Las drogas de amplio espectro como brivaracetam y clobazam son una buena opción en casos de crisis generalizadas y poseen un grado de tolerabilidad muy aceptable. Los nuevos antiepilépticos bloqueadores de canales de sodio, como lacosamida y eslicarbazepina tienen un perfil de efectos adversos más favorable que los bloqueadores de sodio de primera o segunda generación. Estos nuevos medicamentos pueden utilizarse en pacientes con epilepsia de difícil control. Cannabidiol y fenfluramina son muy útiles en el tratamiento del síndrome de Dravet o Lennox Gastaut. La Alopregnenolona y ganaxolona demuestran buena eficacia en casos de estado epiléptico y podrían en el futuro cercano tener un papel importante en este escenario clínico.

Antiepileptic drugs are the first treatment option in patients with epilepsy. Drugs developed after 2000 are known as third generation antiepileptic drugs. These medications offer new mechanisms of action and favorable pharmacokinetics, decreasing the occurrence of side effects and drug-drug interactions. Broad spectrum antiepileptic drugs, such as brivaracetam and clobazam are good choices for generalized tonic colonic seizures and are well tolerated.New sodium channel blockers such as lacosamide and eslicarbazepine, have a more "benign" side effect profile than the first or second generation of sodium channel blockers. These new drugs are useful therapies in patients with epilepsy of difficult control. Cannabidiol and fenfluramine are useful in the treatment of Dravet or Lennox Gastaut syndrome. Allopregnenolona and ganaxolone showed good efficacy in status epilepticus and could play an important future role in this clinical scenario.

Olfactory stimulation induces delayed responses in epilepsy.

Precipitation and inhibition of seizures and epileptic discharges by sensory stimuli are receiving increasing attention because they provide insight into natural seizure generation in human epilepsies and can identify potential nonpharmacological therapies. We aimed to investigate modulation (provocation or inhibition) of epileptiform discharges (EDs) in mesial temporal lobe epilepsy (MTLE) versus idiopathic generalized epilepsy (IGE) by olfactory stimulation (OS) compared with standard provocation methods. The underlying hypothesis was that any response would be more likely to occur in MTLE, considering the anatomical connections of the temporal lobe to the olfactory system. This multicenter, international study recruited patients with either MTLE or IGE who were systematically compared for responses to OS using an EEG/video-EEG protocol including a 30-min baseline, twice 3-min olfactory stimulation with ylang-ylang, hyperventilation, and intermittent photic stimulation. The 95% confidence interval (CI) for the baseline EDs in each patient was calculated, and modulation was assumed when the number of EDs during any 3-min test period was outside this CI. A total of 134 subjects (55 with MTLE, 53 with IGE, and 26 healthy controls) were included. Epileptiform discharges were inhibited during OS in about half the patients with both MTLE and IGE, whereas following OS, provocation was seen in 29.1% of patients with MTLE and inhibition in 28.3% of patients with IGE. Olfactory stimulation was less provocative than standard activation methods. The frequent subclinical modulation of epileptic activity in both MTLE and IGE is in striking contrast with the rarity of reports of olfactory seizure precipitation and arrest. Inhibition during OS can be explained by nonspecific arousal. The delayed responses seem to be related to processing of olfactory stimuli in the temporal lobe, thalamus, and frontal cortex.

Electroclinical features and long-term outcome of cryptogenic epilepsy in children with Down syndrome.

OBJECTIVE: To describe the electroclinical features and the long-term outcomes of epilepsy in a large cohort of males and females with Down syndrome who developed epilepsy in childhood. STUDY DESIGN: Subjects with Down syndrome and cryptogenic epilepsy with onset in childhood were identified retrospectively from the databases of 16 Italian epilepsy centers over a 40-year period. For each subject, age at onset of seizures, seizure semiology and frequency, electroencephalography characteristics, treatment with antiepileptic drugs, and long-term clinical and electroencephalography outcomes were analyzed. RESULTS: A total of 104 subjects (64 males [61.5%], 40 females [38.5%]) were identified. Seizure onset occurred within 1 year of birth in 54 subjects (51.9%), between 1 and 12 years in 42 subjects (40.4%), and after 12 years in 8 subjects (7.7%). Males had a younger age of seizure onset than females. Of the 104 subjects, 51 (49.0%) had infantile spasms (IS), 35 (33.7%) had partial seizures (PS), and 18 (17.3%) had generalized seizures (GS). Febrile seizures were recorded in 5 (4.8%) subjects. Intractable seizures were observed in 23 (22.1%) subjects, including 5 (9.8%) with IS, 8 (44.4%) with PS, and 10 (31.3%) with GS. CONCLUSION: Cryptogenic epilepsy in Down syndrome may develop during the first year of life in the form of IS or, successively, as PS or GS. Electroclinical features of IS resemble those of idiopathic West syndrome, with a favorable response to treatment with adrenocorticotropic hormone seen. Patients experiencing PS and GS may be resistant to therapy with antiepileptic drugs.

Tratamento das epilepsias generalizadas idiopáticas / Idiopathic generalized epilepsies treatment

As epilepsias generalizadas idiopáticas (EGIs) correspondem a um-terço de todas as epilepsias. Apesar desta elevada freqüência, as EGIs permanecem pouco reconhecidas. As características clínicas são fundamentais para o diagnóstico. Neste grupo de epilepsias, todos os tipos de crises generalizadas podem ocorrer especialmente as crises tônico-clônicas generalizadas, as crises mioclônicas e as crises de ausência. O eletroencefograma é bastante sugestivo do diagnóstico quando evidencia os típicos complexos espículas ou poliespículas-onda lenta, generalizados, simétricos e com atividade de base normal. De acordo com o tipo de crise predominante e com a idade de início das crises, as EGIs são divididas em subsíndromes. A importância do diagnóstico preciso está relacionada com a elevada porcentagem de indivíduos livre de crises quando tratados com a medicação antiepiléptica apropriada. Por outro lado, o uso de algumas medicações antiepilépticas como carbamazepina e fenitoína pode exacerbar as crises ou até mesmo induzir estado de mal epiléptico em determinadas subsíndromes. Neste artigo, revisamos as principais medicações antiepilépticas utilizadas no tratamento das EGIs bem como alguns aspectos práticos no tratamento das subsíndromes mais freqüentes.

Idiopathic generalized epilepsies (IGEs) correspond to one-third of all epilepsies. Despite of this high frequency, IGEs remains underdiagnosed. Clinical features are the cornerstone to diagnosis. In this group all types of generalized seizures may occur such as generalized tonic-clonic, absences and myoclonic seizures. EEG is very supportive of IGEs diagnosis when it shows the typical generalized symmetrical, spike or polispyke and waves complexes with normal background. According to the main seizure type and the age of onset, IGEs are divided in subsyndromes. The importance of the correct diagnosis is supported by the high rate of seizure free patients under appropriate antiepileptic drug therapy. On the other hand, the use of some antiepileptic drugs such as carbamazepine or phenytoin may exacerbate the seizures or even induce status epilepticus in some subsyndromes. In this article, the main antiepileptic drugs used in the treatment of IGEs are reviewed as well as some practical issues for IGEs subsyndromes treatment.