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Lacosamide in absence status epilepticus

Open ArchivePublished:January 06, 2014DOI:https://doi.org/10.1016/j.seizure.2013.12.004
      To the Editor
      Although Lacosamide (LCM) has become a widely used drug in patients with status epilepticus,
      • Höfler J.
      • Trinka E.
      Lacosamide as a new treatment option in status epilepticus.
      the role of LCM in patients with idiopathic generalized epilepsy presenting with absence status epilepticus (ASE) is currently unknown.
      A 57-year-old woman came to be under our observation after experiencing confusion and drowsiness, immediately after waking up. Her family history was unremarkable. Apart from mild mental retardation and epilepsy, she had no other medical problems. Rare tonic-clonic seizures, and episodes of lost contact lasting for a few seconds or minutes had occurred monthly since the age of 6 years old despite having been treated with 2000 mg/day valproate (VPA), 300 mg/day lamotrigine (LTG), 3000 mg/day levetiracetam (LEV), 300 mg/day topiramate, 100 mg/day phenobarbital. The interictal EEG showed generalized spike-wave and polyspike-wave discharges at 3–4 Hz, lasting from 1 to 3 s. Brain MRI and genetic analysis (karyotype and array-CGH) were normal. After 6 h from the onset of confusion, the patient was admitted to our centre and at that time she was on 2000 mg/day VPA (plasma VPA was 87 mg/L, range 50–100 mg/L) and 3000 mg/day LEV (plasma LEV was 25 mg/L, range 10–37 mg/L). A long-term video-EEG monitoring was performed and ASE was diagnosed. In particular, she was slow, vague, inattentive, with no verbal contact and displayed rare, small myoclonic twitches of the eyelids and facial muscles. The ictal EEG revealed a continuous, generalized, 2.5–4 Hz spike, polispike-wave pattern and brief trains of polispikes during confusional state (Fig. 1a) . Intravenous (IV) diazepam (10 mg in bolus) induced a rapid but transient effect (Fig. 1b), with ASE reappearing after 5 min. The administration of IV diazepam (10 mg bolus) was also repeated without effect. We therefore administered an IV loading dose of 200 mg LCM over a period of 15 min, through a peripheral line, diluted in 50 ml of normal saline. During and at the end of infusion, the clinical picture and EEG pattern were unchanged (Fig. 1c). After 10 min, an additional 200 mg of LCM was administered for 15 min without effect (Fig. 1d). No adverse effects were observed during the administration of LCM and no ECG and laboratory values-changes were documented. After 24 h the ASE spontaneously resolved. The patient was then given 2000 mg/day VPA and 100 mg/day LTG, while LEV was gradually discontinued. She has now been seizure-free during the 12 months of follow-up.
      Figure thumbnail gr1
      Fig. 1Generalized polispike-and-wave pattern during patient's confusional state (a). IV diazepam induced a transient effect (b), while IV LCM was not effective (c and d).
      Although the most commonly used bolus dose of LCM is 200–400 mg over 3–5 min,
      • Höfler J.
      • Trinka E.
      Lacosamide as a new treatment option in status epilepticus.
      the right dose and the infusion rate needs further clarification. We tried splitting the dose of LCM into two slow infusions of 200 mg to further evaluate the efficacy. Status epilepticus is considered aborted if ictal patterns cease within 20 min following treatment and remains suppressed for 40 min.
      • Treiman D.M.
      • Meyers P.D.
      • Walton N.Y.
      • Collins J.F.
      • Rowan A.J.
      • Handforth A.
      • et al.
      A comparison of four treatments for generalized convulsive status epilepticus.
      Therefore, it is evident that LCM was not effective in our case.
      ASE is a form of non-convulsive status epilepticus characterized by ongoing or intermittent epileptic activity with behavioural and cognitive changes and occurs in idiopathic generalized epilepsy.
      • Treiman D.M.
      Eletroclinical features of status epilepticus.
      ASE has also been evident in adults whose idiopathic generalized epilepsy persists into adulthood and can occur as a consequence of drug withdrawal or other external factors such as sleep deprivation, excessive alcohol intake, menstruation, fever and metabolic disturbances. Finally, inappropriate antiepileptic drugs (especially carbamazepine) can also result in typical or atypical ASE. The EEG demonstrates a pattern of prolonged generalized synchronous 3 Hz spike-wave complexes; however, if ASE continues for several hours or more, the frequency of spike-wave discharges decreases. Variable response of ASE occurs with IV benzodiazepines, while good control with adequate doses of anti-absence drugs, mainly VPA, has been documented. The mechanism underlying the generation of absence seizures is due to an oscillatory activity within a corticothalamic network that depends on GABAergic systems, but especially T-type calcium channels.
      • Mantegazza M.
      • Curia G.
      • Biagini G.
      • Ragsdale D.S.
      • Avoli M.
      Voltage-gate sodium channels as therapeutic targets in epilepsy and other neurological disorders.
      Phenytoin (PHT) and carbamazepine (CBZ) inhibit voltage-gated sodium channels (VGSCs) at therapeutic concentrations and the attenuation of Na+ current is the main mechanism of their efficacy for the treatment of focal and generalized tonic–clonic seizures, but not against absence seizures. In fact, these drugs are ineffective in pentetrazol-treated rodents, a model used to identify drugs that are efficacious for absence seizures. LCM acts primarily by interfering with the slowly inactivating component of voltage-gated sodium currents, without affecting the fast component that is targeted by traditional sodium channel blockers.
      • Höfler J.
      • Trinka E.
      Lacosamide as a new treatment option in status epilepticus.
      Moreover, as with PHT and CBZ, previous experimental evidence in rodent models showed that LCM did not provide protection against seizures provoked by pentylenetetrazol,
      • Mantegazza M.
      • Curia G.
      • Biagini G.
      • Ragsdale D.S.
      • Avoli M.
      Voltage-gate sodium channels as therapeutic targets in epilepsy and other neurological disorders.
      and no effect is observed on voltage-clamped Ca2+ channels (T-, L-, N- or P-type). Consistent with this data, our case confirms that LCM selectively targets VGSCs, showing efficacy for the treatment of focal and generalized tonic-clonic seizures, but not against absence seizures and ASE.

      Conflicts of interest

      The authors declare that there are no conflicts of interest.

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