Pierre Genton

Summary: Few studies focused on the long‐term outcome of Dravet syndrome in adulthood are available in the literature, but all are concordant. In this article, we consider the outcomes of 24 patients followed at the Centre Saint‐Paul, Marseille, up to the age of 50, and compare them to the patients reported in the literature. Five patients (20.8%) died, at a mean age of 24.8 years, one by status epilepticus, three by sudden unexpected death in epilepsy (SUDEP), and one of unknown cause. Epileptic seizures tend to become less frequent and less severe after childhood. Fever sensitivity (temperature variations) persists throughout the clinical course of DS, but its impact on seizure frequency and severity is milder than in infancy. Generalized convulsive seizures, mostly reported as generalized tonic–clonic seizures (GTCS), were the only seizure type observed in almost all of the patients, often with a focal onset. They are less frequent than in childhood and mostly nocturnal. Some of these major convulsive seizures have less typical aspects, for example, bilateral or asymmetric tonic posturing, followed in some cases by a tonic vibratory state or clonic movements (Oguni et al., Brain Dev 2001;23:736–748; Akiyama et al., Epilepsia 2010;51:1043–1052). Other seizures like myoclonic seizures, atypical absences, and complex partial seizures (CPS) are less common in adulthood: Among our 24 patients, only 6 had atypical absences, and one myoclonic and one complex focal seizures. Electroencephalography (EEG) also changes with age but is still multiple and heterogenous, interictally and ictally. Photosensitivity and pattern sensitivity also showed a tendency to disappear before the age of 20. Motor abnormalities are common. Cerebellar features, including ataxia, dysarthria, intention tremor, and eye movement disorder, become more prominent. Walking is markedly impaired, often due to orthopedic signs such as kyphosis, kyphoscoliosis, flat feet, or claw feet. This symptomatology was minor during childhood and worsened during and after adolescence, despite physiotherapy. Mental retardation ranged from moderate to severe, with predominance of language impairment, and some patients had a major personality disorder, labeled autistic or psychotic. Dependency in adulthood is nearly constant: Only 3 of our 24 adult patients lived independently.

Summary: Purpose: Absence status epilepticus (AS) is a prolonged, generalized, and nonconvulsive seizure that may occur in various circumstances. We report a series of patients in whom recurrent, unprovoked, typical AS was the main clinical feature.Method: We retrospectively reviewed consecutive patients referred to our epileptic centers, on the following criteria: (1) recurrent, unprovoked episodes of typical AS representing the unique or the predominant seizure type, (2) at least one episode of AS recorded by video‐EEG or by EEG only, and (3) clinical and EEG features fulfilling the criteria of idiopathic epilepsy. We excluded patients with situation‐related AS.Results: We found 11 such cases (5F, 6M). The onset of AS was after puberty or in early adulthood in most; no clear triggering factor could account for the recurrence of AS episodes; infrequent generalized tonic–clonic seizures, and, rarely, absences, could also occur. These patients had no family history of epilepsy, normal neurological evaluation, normal neuroimaging, interictal EEG showing generalized spike‐ and polyspike‐wave discharges on a normal background, no photoparoxysmal response, variable response of AS to intravenous benzodiazepines, and usually good seizure control with valproate. This peculiar condition was misdiagnosed in most because of the unusual clinical presentation and of some atypical interictal EEG findings, often leading to the use of inappropriate drugs.Conclusion: Although there is some overlap with previously described epilepsy syndromes, specific and shared features point to the existence of a distinct epilepsy entity that we propose to name “absence status epilepsy.” This syndrome expands the spectrum of idiopathic generalized epilepsies.

To prospectively assess the safety and efficacy of levetiracetam in patients with uncontrolled focal epilepsy, in a common practice-based setting. In this phase IV, open-label, 16-week community-based study, adult patients with focal seizures initially received levetiracetam 1,000 mg/day. Throughout the study, the dose was adjusted in increments of 1,000 mg (maximum 3,000 mg/day) to achieve seizure control and maintain tolerability. The outcome parameters were the percentage reduction in partial and total seizure frequency per week from historical baseline, global evaluation scale (GES), and adverse events (AE). Seven hundred and thirty-one patients were included in this analysis and 84.4% completed the study. The median percent reduction in all seizures was 47.8%, and 49.3% for all partial seizures. The 50% responder rate was 49%, and the seizure-free rate was 17.2% for all partial seizures. Approximately 60% of patients showed moderate to marked improvement on the GES. The majority of AE were of mild to moderate severity; the most commonly reported being asthenia, somnolence, headache, and dizziness. Levetiracetam is both efficacious and safe as an add-on therapy in patients with refractory epilepsy treated by clinicians in their daily practice.

Among the epileptic syndromes that are defined mainly on the basis of a characteristic seizure type, epilepsy with myoclonic absences (EMA) stands out as a somewhat controversial entity. This is...

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.