Seizure 25 (2015) 32
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Letter to the Editor Lacosamide in absence status epilepticus: Effective or ineffective?
Keywords: Lacosamide Absence status epilepticus
To the Editor, We read with great interest the letter of Sodemann et al.1 on successful treatment of a patient with refractory absence status epilepticus (ASE) with lacosamide (LCM). In particular, Sodemann et al. reported the case of a 64-year-old male with juvenile absence epilepsy (he was on 400 mg/day lamotrigine, 400 mg/day topiramate and 2500 mg/day levetiracetam; plasma concentrations were not investigated) and an ASE treated with intravenous (IV) diazepam (10 mg, rapid but short lasting effect), IV levetiracetam (1000 mg, transient effect with ASE reoccurring after 3 h), and, finally, IV LCM (400 mg over a period of 30 min, complete recovery less than 2 h later). LCM was considered effective in this case. We recently reported the first episode of a treatment of ASE with IV lacosamide.2 The patient was already on large doses of levetiracetam (3000 mg/ day, plasma levetiracetam was 25 mg/L, range 10–37 mg/L) and valproate (2000 mg/day, plasma valproate was 87 mg/L, range 50– 100 mg/L), and had only a partial response to IV 20 mg diazepam. Unfortunately 400 mg of IV LCM was not effective (plasma LCM after infusion was 8.2 mg/L, range 1–10 mg/L) in the termination of the status epilepticus (after 24 h ASE spontaneously resolved). Is LCM effective or ineffective in ASE? There are different criteria for the effectiveness of an antiepileptic drug in the termination of status epilepticus in the literature.3 The most common specification was termination of seizures within 30 min of infusion; nevertheless, other definitions include 3 min, 15 min, 20 min, 1 h, 12 h, 24 h and 48 h.3 In our patient, we utilized Treiman et al. criteria4: status epilepticus is considered aborted if ictal patterns cease within 20 min following treatment and remain suppressed for 40 min. According to these outcome criteria, LCM was not effective in our case, but also in Sodemann et al. patient, and the good outcome in these cases was probably due to the known good prognosis of ASE.5 Nevertheless, in the light of the different criteria for the effectiveness, a call for a definition of response to the intervention in status epilepticus is needed. The mechanism underlying the generation of absence seizures is due to a oscillatory activity within a corticothalamic network that depends on GABAergic systems, but especially T-type calcium channels.6 LCM acts primarily by interfering with the slowly inactivating component of voltage-gated sodium currents, and no
effect was observed on voltage-clamped Ca2+ channels (T-, L-, N- or P-type). Consistent with this data, LCM should show efficacy for the treatment of focal and generalized tonic–clonic seizures, but not against absence seizures and ASE. Moreover, in our small experience (one patient with ASE, two patients with juvenile absence epilepsy, and three patients with juvenile myoclonic epilepsy; data unpublished) LCM was ineffective in the treatment of absence seizures. It is, nevertheless, evident that randomized controlled trials are needed to establish the therapeutic effect of LCM in the treatment of ASE and absence seizures. Authors contribution Giuseppe d’Orsi, Maria Grazia Pascarella, Tommaso Martino, Luigi M. Specchio: analysis and interpretation of the manuscript. Conflict of interest None declared. References 1. Sodemann U, Moller HS, Blaabjerg M, Beier CP. Successful treatment of refractory absence status epilepticus with lacosamide. J Neurol 2014;261(10):2025–7. 2. d’Orsi G, Pacillo F, Trivisano M, Pascarella MG, Ferrara MA, Specchio LM. Lacosamide in absence status epilepticus. Seizure 2014;23:397–8. 3. Yasiry Z, Shorvon S. The relative effectiveness of five antiepileptic drugs in treatment of benzodiazepine-resistant convulsive status epilepticus: a metaanalysis of published studies. Seizure 2014;23:167–74. 4. Treiman DM, Meyers PD, Walton NY, Collins JF, Colling G, Rowan AJ, et al. A comparison of four treatments for generalized convulsive status epilepticus. N Engl J Med 1998;17(339 (12)):792–8. 5. Scholtes FB, Renier WO, Meinardi H. Non-convulsive status epilepticus: causes, treatment, and outcome in 65 patients. J Neurol Neurosurg Psychiatry 1996;61: 93–5. 6. Mantegazza M, Curia G, Biagini G, Ragsdale DS, Avoli M. Voltage-gate sodium channels as therapeutic targets in epilepsy and other neurological disorders. Lancet Neurol 2010;9:413–24.
Giuseppe d’Orsi* Maria Grazia Pascarella Tommaso Martino Luigi M. Specchio Epilepsy Centre – Clinic of Nervous System Diseases, University of Foggia, Ospedali Riuniti, Foggia, Italy *Corresponding author at: Department of Neurological Sciences, Epilepsy Centre – Clinic of Nervous System Diseases, University of Foggia, Ospedali Riuniti, Via Luigi Pinto 1, 71100 Foggia, Italy. Tel.: +39 0881 736125; fax: +39 0881 732553 E-mail address:
[email protected] (G. d’Orsi).
http://dx.doi.org/10.1016/j.seizure.2014.11.012 1059-1311/ß 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
25 November 2014
