Use of Lamotrigine in Lennox-Gastaut and Related Epilepsy Syndromes

Dulac, Olivier; Kamińska, Anna

doi:10.1177/0883073897012001071

Cited by 41 publications

(19 citation statements)

References 27 publications

(10 reference statements)

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“…In addition, although the combination of valproate and lamotrigine is favored by some as a synergistic combination in this condition [20,21], lamotrigine should be used cautiously in MAE especially in children with frequent myoclonic seizures since it can worsen this seizure type [11]. …”

Section: Discussionmentioning

confidence: 99%

Paradoxical exacerbation of myoclonic-astatic seizures by levetiracetam in myoclonic astatic epilepsy

et al. 2015

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BackgroundLevetiracetam is a broad spectrum antiepileptic drug (AED) with proven efficacy when used as adjunctive therapy against myoclonic seizures. We report two patients suffering from epilepsy with myoclonic-astatic epilepsy (MAE) who experienced a paradoxical worsening of seizures after initiation of treatment with LEV, a finding not previously described.Case presentationPatients included were enrolled in an ongoing large prospective study evaluating children and adults with new onset epilepsy in Lebanon conducted at the American University of Beirut Medical Center in association with the Lebanese Chapter of the International League against Epilepsy. Based on an extensive evaluation, these patients were stratified into idiopathic partial, idiopathic generalized, symptomatic partial or symptomatic generalized epilepsies. Whenever possible the electroclinical syndrome was identified according to the ILAE classification of epilepsy syndromes. Patients were subsequently followed up on regular intervals and were assessed for adverse events, and seizure recurrence.MAE was diagnosed in five (1.6%) out of 307 consecutive children enrolled in this study. LEV was used as adjunctive therapy in four of those children with two experiencing a substantial and dose related worsening in the frequency of their myoclonic and atonic seizures.ConclusionLEV should be used with caution in children with MAE and an exacerbation of seizure frequency temporally related to the introduction of LEV should alert the clinician to the possibility of a paradoxical seizure exacerbation.

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Section: Discussionmentioning

confidence: 99%

Paradoxical exacerbation of myoclonic-astatic seizures by levetiracetam in myoclonic astatic epilepsy

et al. 2015

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“…For resistant to valproate or benzodiazepines. [64] However, lamotrigine example, carbamazepine or vigabatrin may improve tonic seizures should be used with caution in epilepsies featuring myoclonic but worsen atypical absences. [59] Benzodiazepines may have a seizures because aggravation of this condition has been reportwide spectrum of action but may induce somnolence which, in ed.…”

Section: Lennox-gastaut Syndromementioning

confidence: 99%

Valproate as a Mainstay of Therapy for Pediatric Epilepsy

Guerrini

2006

Pediatric Drugs

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This article reviews relevant pharmacologic and clinical information gathered for valproate since it was introduced into clinical practice 37 years ago and the application of this information for the treatment of childhood epilepsy. Valproate is available for oral and parenteral use. Oral forms are almost completely bioavailable but the rate of absorption varies between formulations. The Chrono tablet formulation has not been adapted for children aged <6 years, in whom the oral solution or syrup, requiring two or three daily administrations, has been used until recently. A new formulation specifically adapted for children, Chronosphere, administrated once or twice daily, is a modified-release formulation of valproate that minimizes fluctuations in serum drug concentrations during a dosage interval. Plasma protein binding is 80-94% and tends to decrease with increasing drug concentration. Valproate elimination is markedly decreased in newborns compared with older children and adults. Elimination by glucuronidation only becomes fully effective by the age of 3-4 years. In children aged 2-10 years receiving valproate, plasma clearances are 50% higher than those in adults. Over the age of 10 years, pharmacokinetic parameters approximate those of adults. Valproate can increase plasma concentrations of concomitant drugs, such as phenobarbital and lamotrigine, by inhibiting their metabolism. As a result of its broad spectrum of efficacy in a wide range of seizure types and epilepsy syndromes, valproate is a drug of choice for children with newly diagnosed epilepsy (focal or generalized), idiopathic generalized epilepsy, epilepsies with prominent myoclonic seizures or with multiple seizure types, and photosensitive epilepsies. In the group of cognitive epilepsies, in which severe spike and wave discharges are accompanied by cognitive deterioration, valproate, ethosuximide, or both should be tested before using corticosteroids. In comparative trials with carbamazepine, phenytoin, and phenobarbital in focal epilepsy and with ethosuximide in absence epilepsy, valproate was as effective and showed a favorable tolerability profile, with minimal adverse cognitive and CNS effects. The low potential for paradoxical seizure aggravation and the long-term efficacy of the drug are additional important factors that contribute to its excellent profile. Intravenous valproate may be effective for the treatment of convulsive and non-convulsive status epilepticus that is refractory to conventional drugs. In infants, potential benefits should be carefully weighed against the risk of liver toxicity. Gastrointestinal intolerance is a relatively frequent, dose-related adverse effect of the drug in children. Bodyweight increase and tremor may be observed in older children and adolescents. Despite the challenge of newer drugs, valproate remains a gold standard antiepileptic drug for the treatment of children.

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“…From the early 1990s, apparent efficacy in open-label studies (Timmings et al 1992; Schlumberger et al 1994; Donaldson et al 1997; Farrell et al 1997) in LGS led to double-blind, randomized clinical trials (Motte et al 1997; Eriksson et al 1998), confirming a statistically significant improvement, at least in major seizures. Worsening or no improvement of myoclonic jerks has been reported in LGS (Donaldson et al 1997; Dulac and Kaminska 1997) and related syndromes.…”

Section: Chronic Medical Treatmentmentioning

confidence: 99%

Treatment of Lennox-Gastaut syndrome: overview and recent findings

Rijckevorsel¹

2008

NDT

118

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Lennox-Gastaut syndrome (LGS) is a rare, age-related syndrome, characterized by multiple seizure types, a specifi c electro-encephalographic pattern, and mental regression. However, published data on the etiology, evolution, and therapeutic approach of LGS are contradictory, partly because the precise defi nition of LGS used in the literature varies. In the most recent classifi cation, LGS belongs to the epileptic encephalopathies and is highly refractory to all antiepileptic drugs. Numerous treatments, medical and non-medical, have been proposed and results mostly from open studies or case series have been published. Sometimes, patients with LGS are included in a more global group of patients with refractory epilepsy. Only 6 randomized double-blind controlled trials of medical treatments, which included patients with LGS, have been published. Overall, treatment is rarely effective and the fi nal prognosis remains poor in spite of new therapeutic strategies. Co-morbidities need specifi c treatment. This paper summarizes the defi nition, diagnosis and therapeutic approach to LGS, including not only recognized antiepileptic drugs, but also "off label" medications, immune therapy, diet, surgery and some perspectives for the future.

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Use of Lamotrigine in Lennox-Gastaut and Related Epilepsy Syndromes

Cited by 41 publications

References 27 publications

Paradoxical exacerbation of myoclonic-astatic seizures by levetiracetam in myoclonic astatic epilepsy

Paradoxical exacerbation of myoclonic-astatic seizures by levetiracetam in myoclonic astatic epilepsy

Valproate as a Mainstay of Therapy for Pediatric Epilepsy

Treatment of Lennox-Gastaut syndrome: overview and recent findings

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