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| TOPIC OF THE ISSUE-EDITORIAL |
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| Year : 2011 | Volume
: 59
| Issue : 1 | Page : 51-52 |
Seizure aggravation with antiepileptic drugs in idiopathic generalized epilepsies
JMK Murthy
Department of Neurology, The Institute of Neurological Sciences, CARE Hospital, Nampally, Hyderabad, India
| Date of Submission | 29-Jan-2011 |
| Date of Decision | 29-Jan-2011 |
| Date of Acceptance | 29-Jan-2011 |
| Date of Web Publication | 18-Feb-2011 |
Correspondence Address:
JMK Murthy
Department of Neurology, The Institute of Neurological Sciences, CARE Hospital, Exhibition Road, Nampally, Hyderabad - 500 001
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0028-3886.76858
How to cite this article:
Murthy J. Seizure aggravation with antiepileptic drugs in idiopathic generalized epilepsies. Neurol India 2011;59:51-2 |
Idiopathic generalized epilepsies (IGE) are a group of genetically determined epilepsies and affect otherwise normal people and manifest with typical absences, myoclonic jerks, and generalized tonic-clonic seizures, either alone or in varying combinations and severity. Aggravation of seizures in IGE syndromes by antiepileptic drugs (AEDs) is increasingly recognized as a serious and common problem. [1],[2] Seizure aggravation is considered to be a paradoxical reaction when an AED increases the frequency and/or changes the pattern of a seizure type against which it is usually effective, or when it leads to the onset of new types of seizures. [3],[4] This usually occurs in the usual doses and normal serum levels and in the absence of any other clinical features suggestive of an encephalopathy or sedation. [5] Clinical improvement occurs after dose reduction.
In this issue of the journal, Menon and colleagues [6] report oxacarbazepine induced myoclonic seizures associated with worsening of EEG abnormalities in a patient of Jeavons syndrome. Paradoxical aggravation in IGE usually results in subtle or overt increased seizures with or without new seizure types [2],[4],[5],[7],[8],[9],[10] associated with worsening of EEG abnormalities. [2],[11],[12] Severe aggravation of seizures in IGE may result in absence or myoclonic status epilepticus, [2],[13],[14],[15] often with atypical clinical and EEG features. [2]
This inverse pharmacodynamic reaction in the presence of a drug serum level within the "therapeutic" range and in the absence of any other clinical features suggestive of an encephalopathy or sedation occurs with AEDs with a single mechanism of action, either GABAergic enhancement (vigabatrin, tiagabine, gabapentin) or blockade of Na + channels (carbamazepine, oxcarbazepine, phenobarbital, phenytoin, lamotrigine). AEDs with multiple mechanisms of action are less likely to aggravate seizures. [1],[16] Consistent evidence of paradoxical reaction has been shown with the use of carbamazepine in IGEs with absence seizures or myoclonic seizures. [1] Other drugs associated with aggravation or precipitation of typical absences and myoclonic seizures include oxcarbazepine, phenytoin, tiagabine, vigabatrin, and pregabalin. [2],[16] Carbamazepine, oxcarbazepine, phenytoin, lamotrigine, and gabapentin can increase myoclonic seizures in patients with juvenile myoclonic epilepsy. [2],[10],[16]
Cellular mechanisms involved in the paradoxical reaction of AEDs are different for GABAergic and sodium channel blockers. In a genetic absence rat model, GABAergic drugs increase spike-wave discharges and clinical seizures. [17] This phenomenon is related to the GABA-induced hyperpolarization of thalamic neurons, enhancing oscillatory thalamocortical activity. [18] Sodium channel blockers enhance membrane stabilization, a property that may indirectly increase hypersynchronization of neuronal discharges in a thalamocortical loop already showing intensified oscillatory activity. This may result in facilitation of generalized epileptogenesis. [19]
This pharmacodynamic AED-induced seizure aggravation in IGE can potentially be avoided by careful syndrome diagnosis and determining the seizure type. It may be appropriate to avoid in patients with IGE, AEDs with a single mechanism of action, either GABAergic enhancement or blockade of Na + channels.
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