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

Abstract

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.

Seizure Aggravation Following Adjunctive Levetiracetam Therapy in Children with Epilepsy: a Single Tertiary Center Experience

“…LEV-associated seizure aggravation was also reported in other studies (Table 3) [6][7][8][9][10] . Seizure aggravation associated with LEV has been reported in patients with absence seizures 6) , continuous spikes and waves during slow sleep 7) , myoclonic seizures 17) , myoclonic-astatic seizures 8) , and refractory epilepsy 9) . To date, there is insufficient evidence that LEV induces seizure aggravation in patients with certain seizure types or syndromes.…”

“…There have been many reports of AED-associated seizure worsening in recent decades [5][6][7][8][9][10][15][16][17][18][19][20][21] . Unfortunately, they provided with certain types of epilepsy 5,15,19) .…”

“…Drugs that can have this effect include phenytoin (PHT) and phenobarbital (PB). Worsening 9) 2003 Adults -14 (18%) Various Refractory epilepsy Auriel et al 14) 2007 Adults -4 (8%) Various Refractory epilepsy, add-on therapy Szűcs, et al 10) 2008 Adults -31 (14%) Various Intellectual disability Caraballo, et al 7) 2010 Children -2 LTG, PB CSWSS Auvin, et al 6) 2011 Children -6 ESM, VPA, LTG Absence seizures Aivazian, et al 13) 2011 Children -11 (5.7%) Various Add-on therapy Liu, et al 23) 2012 Children -3 None Myoclonic seizures Makke, et al 8) 2015 Children - 19) . Paradoxical reactions can be described by paradoxical pharmacodynamic effects at nontoxic serum levels: that is, the drug aggravates rather than reduces seizures 21) .…”

“…While LEV has come into general use, there are only a few case reports linking it to seizure aggravation [6][7][8][9][10] . To date, the studies regarding the prevalence and risk factors of seizure aggravation caused by LEV have been rare.…”

Perampanel for the treatment of patients with myoclonic seizures in clinical practice: Evidence from the PERMIT study

“…Valproate and benzodiazepines, such as clonazepam, have historically been used to treat myoclonic seizures, and work by enhancing γ-aminobutyric acid activity in the brain [5]. Levetiracetam is also used to treat myoclonic seizures [2,[7][8][9], although there have been reports of myoclonic seizure exacerbation in some patients [10][11][12]. In addition, there are a few reports showing some effectiveness of zonisamide [13,14] and topiramate [15], but side effects have been reported.…”