Lennox-Gastaut syndrome with late-onset and prominent reflex seizures in trisomy 21 patients.

PURPOSE: Lennox-Gastaut syndrome (LGS) is a severe epileptic condition characterized by multiple seizure types including tonic seizures, slow spike-and-wave discharges on electroencephalography (EEG), and cognitive impairment. LGS can occur in apparently healthy subjects or in patients with preexisting brain damage. The onset peaks between 3 and 5 years of age and the prognosis is usually poor. Herein we report 13 subjects with trisomy 21 who developed LGS. METHODS: We retrospectively reviewed the clinical and EEG data of consecutive patients with LGS and trisomy 21 referred to five epilepsy centers over the last 30 years. RESULTS: Data for 13 patients (8 male, 5 female) were collected. The mean age at onset was 9.1 years (range 5-16). The mean age at last follow-up was 23.5 years (range 11-43 years). Seizure onset was after age 8 years in eight (62%) patients and between age 5 and 8 in the other five. In none of the cases did a West syndrome precede the onset of LGS. Nine of 13 patients (69%) had unambiguous reflex seizures, mostly precipitated by sudden unexpected sensory stimulations, usually preceding or accompanying the onset of a full-blown LGS picture. Interictal and ictal EEG findings were typical for LGS. All patients were drug-resistant. DISCUSSION: Patients with trisomy 21 may present a peculiar LGS, characterized by late onset and high occurrence of reflex seizures. Mechanisms underlying this particular presentation of LGS may include dendritic rarefaction and decreased interneurons, as well as functional abnormalities leading to overall decreased brain inhibition in these patients.

Valproic acid in epilepsy : pregnancy-related issues.

Valproic acid (sodium valproate) is widely used as a first-line antiepileptic agent. As with many antiepileptic drugs, there are a number of consequences associated with the use of valproic acid in women of child-bearing potential. Most pregnancies have a favourable outcome in women with epilepsy, and these women should not be discouraged from becoming pregnant. Unlike many other antiepileptic drugs, valproic acid has no significant pharmacokinetic interactions with the steroid hormones used in oral contraceptives. During pregnancy, the major risks to mother and child result from loss of seizure control on the one hand, and an elevated risk of major congenital malformations due to antiepileptic drug treatment on the other. In particular, an elevated risk of major congenital malformations associated with valproic acid use has been a consistent finding in studies of patient registries and several large case series. In addition, developmental delay, characterised by low verbal IQ, has also been reported in children exposed to valproic acid in utero, although the relative risk is not precisely known. For these reasons, pregnancies in women being treated with valproic acid need to be planned, and the benefit-risk ratios associated with continuing valproic acid or changing treatment need to be discussed with the patient. When treatment with valproic acid is the most appropriate treatment to achieve optimal seizure control, a number of measures can be implemented to minimise risk to the fetus. These include the use of the lowest possible effective dose of valproic acid in monotherapy (ideally <1000 mg/day), appropriate folic acid supplementation and close antenatal monitoring. Regular counselling is a prerequisite for informed planning of pregnancies and optimisation of the probability of a healthy outcome. Future research on valproic acid and pregnancy should involve risk assessment in large, population-based prospective studies.

Lack of efficacy and potential aggravation of myoclonus with lamotrigine in Unverricht-Lundborg disease.

PURPOSE: Unverricht-Lundborg disease (ULD) is a progressive myoclonus epilepsy with tonic-clonic seizures, action myoclonus, mild ataxia, without dementia. Persistence of invalidating action myoclonus is a major problem. Drugs like phenytoin can aggravate ULD. In this study, we retrospectively analyzed the effect of add-on lamotrigine (LTG) in the five patients under our care who received LTG. METHOD: Three men and two women, aged 20-50 years who had ULD confirmed by molecular biology, followed in two epilepsy centers, received add-on LTG at 50-300 mg/d. All of them had valproate. The other drugs used in cotherapy were high-dose piracetam, benzodiazepines phenobarbital, topiramate, and primidone. The assessment of LTG was based on detailed interview and clinical examination. Aggravation was diagnosed when myoclonic jerks (MJ) increased without irregular intake of medication, inappropriate lifestyle, encephalopathic or metabolic complications, or overdosage. RESULTS: In two patients, LTG exacerbated MJ in a dose-dependent manner. In one patient, a delayed, severe exacerbation of myoclonus occurred that only ceased after LTG withdrawal and introduction of levetiracetam. These three patients had minor forms of ULD. In two patients with moderate to severe forms of ULD, LTG had no effect. CONCLUSION: Although symptoms may fluctuate in ULD, it was possible to pinpoint lack of improvement (2/5), dose-related exacerbation of myoclonus (2/5), and putative late-onset aggravation (1/5) in five patients treated with adjunctive LTG. LTG does not appear to be a sensible treatment option in ULD.

Epilepsy and women's issues: an update.

Although the fundamentals of epilepsy are similar for both males and females, the clinical management of epilepsy in women should take into consideration a variety of factors including: social and cultural issues, age, relationships, diagnosis and characterization, female specific syndromes, the influence of female hormones, hormonal contraceptives and hormonal replacement therapy, the cosmetic side effects of epilepsy treatment, fertility, pregnancy and child care. Regarding the issue of reproduction, there are several misconceptions in relation to fertility in women with epilepsy. In general, women with epilepsy do not have a markedly reduced fertility compared with those without. Standard AEDs in common use have been associated with an increased risk of foetal malformations and with newer AEDs there is very little information regarding teratogenicity. The incidence of congenital malformations is also known to increase with the number of AEDs. Before planning a pregnancy it is imperative that the best possible seizure control is achieved at the lowest possible AED dose, preferably in monotherapy. With this in mind, the importance of effective pre-pregnancy counselling should be stressed and along with appropriate patient management and folic acid supplementation, effective patient education, most women with epilepsy can lead normal lives and deliver healthy children. This report will provide an update on these important considerations for women with epilepsy from both a social and medical perspective.