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Tiagabine-Induced Absence Status in Idiopathic Generalized Epilepsy

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Tiagabine-Induced Absence Status in Idiopathic Generalized Epilepsy CORE Metadata, citation and similar papers at core.ac.uk Provided by Elsevier - Publisher Connector Seizure 1999; 8: 314–317 Article No. seiz.1999.0303, available online at http://www.idealibrary.com on CASE REPORT Tiagabine-induced absence status in idiopathic generalized epilepsy S. KNAKE, H. M. HAMER, U. SCHOMBURG, W. H. OERTEL & F. ROSENOW Philipps-University, Neurologische Klinik, Marburg, Germany Correspondence to: Dr S. Knake, Neurologische Klinik, Philipps-University, Marburg, Rudolf-Bultmann-Straße 8, 35039 Marburg, Germany Several medications such as baclofen, amitriptyline and even antiepileptic drugs such as carbamazepine or vigabatrin are known to induce absence status epilepticus in patients with generalized epilepsies. Tiagabine (TGB) is effective in patients with focal epilepsies. However, TGB has also been reported to induce non-convulsive status epilepticus in several patients with focal epilepsies and in one patient with juvenile myoclonic epilepsy. In animal models of generalized epilepsy, TGB induces absence status with 3–5 Hz spike-wave complexes. We describe a 32-year-old patient with absence epilepsy and primary generalized tonic–clonic seizures since 11 years of age, who developed her first absence status epilepticus while treated with 45 mg of TGB daily. Administration of lorazepam and immediate reduction in TGB dosage was followed by complete clinical and electroencephalographic remission. This case demonstrates that TGB can induce typical absence status epilepticus in a patient with primary generalized epilepsy. Key words: absence status; status epilepticus; generalized epilepsy; seizure induction; tiagabine. INTRODUCTION wave discharges increased in rats when treated with TGB12–14. Absence status epilepticus is defined as a generalized In addition, TGB was also reported to induce non- absence seizure lasting for more than half an hour in convulsive status epilepticus in several patients with the context of a primary generalized epilepsy1. Dur- partial epilepsy15, 16 and in one patient with juvenile ing the time of mental clouding of differing degree, myoclonic epilepsy6. There have been no detailed re- bilateral synchronous spike-wave discharges can be ports of this effect of TGB in patients with absence recorded by EEG. Of all the forms of non-convulsive epilepsy. status epilepticus, generalized absence status is the We describe a 32-year-old patient with absence most commonly encountered2. The incidence of ab- epilepsy and generalized tonic–clonic seizures since sence status in patients with absence epilepsy is esti- the age of 11 years, in whom TGB induced her first mated to be between 2 and 10%3. absence status. Several antiepileptic drugs have been reported to induce absence status in patients and animal models. Tiagabine (TGB) inhibits the reuptake of CASE REPORT γ -aminobutyric acid (GABA) into the presynaptic terminals and glia cells, thereby making more GABA A 32-year-old woman was admitted with absence sta- available at the synapses4. It increases the extracellular tus epilepticus lasting for more than 6 hours. concentration of GABA after oral administration5, 6. In At the age of 11 years, she began having absences clinical trials TGB had a dose-related anticonvulsant and generalized tonic–clonic seizures. The diagno- effect in patients with focal epilepsies7–11. However, sis of absence epilepsy was supported by generalized in animal models the frequency of interictal spike- spike-wave complexes during hyperventilation and a ∗ E-mail: [email protected] positive family history for epilepsy. Seizures were 1059–1311/99/050314 + 04 $12.00/0 c 1999 BEA Trading Ltd Tiagabine-induced absence status in idiopathic generalized epilepsy 315 Fp1-A1 F7-A1 T3-A1 T5-A1 Fp2-A2 F8-A2 T4-A2 T6-A2 F3-A1 C3-A1 P3-A1 O1-A1 F4-A2 C4-A2 P4-A2 O2-A2 Fz-A2 Pz-A2 Resp EKG 1 s 200 V Fig. 1: Thirty-two-year-old patient with absence status epilepticus lasting for more than 6 hours. This figure shows the EEG on admission. refractory to valproate, primidone, lamotrigine, and responded slowly but adequately to other questions. clonazepam as monotherapy and in several combina- Within the previous 5 days before admission, she had tions. Initially, she had two to three absences per week three similar episodes with mental clouding lasting and one generalized tonic–clonic seizure every two more than 4 hours each. She had never experienced months. She has not experienced any absence seizures absences lasting for more than a minute before treat- and the frequency of generalized tonic–clonic seizures ment with TGB. declined to two per year since she was started on anti- The EEG on admission revealed absence status convulsants. epilepticus (Fig. 1) with generalized spike-wave com- Lamotrigine was discontinued due to nausea and plexes. Initially, she was given 600 mg of sodium- TGB was added to sodium valproate by her neurolo- valproate intravenously to booster the levels, however, gist. The dosage of valproate remained unchanged. without any effect. After administration of 1 mg lo- Routine EEGs were normal except for short bursts of razepam, the EEG and the clinical picture rapidly nor- generalized spike-wave discharges under hyperventi- malized. lation. Tiagabine was discontinued because a status epilep- In the first 6 months, up to a daily dosage of 30 mg, the patient tolerated the new medication well and was ticus inducing effect was suspected. The EEG re- seizure-free except for one generalized tonic–clonic mained normal thereafter. The patient was discharged seizure shortly after initiation of TGB therapy. There- on 2400 mg of sodium valproate. No further status fore, the dose of TGB was increased to 45 mg/d at the epilepticus occurred on follow-up 6 months later. next follow-up visit. Within days, the patient repeat- edly started to feel dizzy and experienced episodes of ‘lack of memory’. At this time, the EEG revealed in- DISCUSSION termittent generalized slowing and spike-wave com- plexes during 30% of the recording. We report a patient with generalized epilepsy who de- On admission, the patient was treated with 2400 mg veloped EEG deterioration and her first absence sta- valproate and 45 mg TGB. The serum level of val- tus epilepticus while taking TGB. Besides the tempo- proate was 74 mg/l. She was admitted for an episode ral relation and the complete EEG normalization after lasting for more than 6 hours, during which she stared discontinuation of TGB, several additional lines of ev- and reacted slowly. She was unable to do simple cal- idence support that TGB induced the status epilepticus culations (e.g. 3 3) but was fully oriented. She in this patient and suggest a GABA-ergic mechanism. × 316 S. Knake et al. Observations in humans 3. Rothner, A. D. and Morris, H. H. Generalized status epilep- ticus. In Epilepsy. Electroclinical Syndromes,Luders,¨ H. and Lesser, R. P. eds., 1987; pp. 207–222. Berlin, Heidelberg, TGB was reported to induce non-convulsive status Springer-Verlag. epilepticus in several patients with focal epilepsies and 4. Fischer, R. Newer antiepileptic drugs. In The Treatment of in one patient with juvenile myoclonic epilepsy6, 15–17. Epilepsy. Principles and Practice, Wyllie, E. ed., 1993; pp. Other GABA-ergic medications such as baclofen or 923–925. Baltimore, Williams and Wilkins. 18–22 5. Fink-Jensen, A., Suzdak, P. D., Swedbweg, M. D. et al. vigabatrin have been reported to induce absence The gamma-aminobutyric acid (GABA) uptake inhibitor, status epilepticus in humans. tiagabine, increases extracellular brain levels of GABA in awake rats. European Journal of Pharmacology, 1992; 220: 197–201. 6. Walton, N. Y., Gunawan, S. and Treiman, D. Treatment of ex- Animal data perimental status epilepticus with the GABA uptake inhibitor, tiagabine. Epilepsy Research, 1994; 19: 237–244. In several animal models of absence epilepsy (i.e. a se- 7. Chadwick, D., Richens, A., Duncan, J. et al. Tiagabine HCl: lective strain of Wistar rats (WAG/Rij-rats) or genetic safety and efficacy as adjunctive treatment for complex partial seizures. Epilepsia, 1991; 32: 20. absence epilepsy rats of Strasbourg (GAERS)), proab- 8. Rowan, J., Uthman, B., Ahman, P. et al. Safety and efficacy of sence effects of vigabatrin and TGB have been demon- three dose levels of tiagabine HCl versus placebo as adjunctive strated6, 12, 23. After administration, TGB enhanced the treatment for complex partial seizures. Epilepsia, 1994; 35: 54. duration and the number of spike-wave discharges 9. Sachedo, R., Leroy, R., Krauss, G. et al. Safety and efficacy 12 of bid and qid dosing with tiagabine HCl versus placebo as in a dose-related fashion . Furthermore, an unusual adjunctive treatment for partial seizures. Neurology, 1995; 45: second type of spike-wave discharges was recorded A202. during the treatment with TGB. These were consid- 10. Uthman, B. M., Rowan, A. J., Ahman, P. A. and Leppik, I. ered to be forerunners of the genuine spike-wave dis- E. Tiagabine for complex partial seizures: a randomized, add- 13 on, dose-response trial. Archives of Neurology, 1998; 55: 56– charges . At a higher TGB dosage, seven of 10 nor- 62. mal animals developed behavioural hyporeactivity and 11. Leppik, I. E. Tiagabine: the safety landscape. Epilepsia, 1995; simultaneously generalized 3–5 Hz spike-wave dis- 36: S10–S13. charges6. 12. Coenen, A. M. L., Blezer, E. H. M. and Van Luijtelaar, E. L. J. M. Effects of the GABA-uptake inhibitor tiagabine GABA plays an important role in the pathophysi- on electroencephalogram, spike-wave discharge and behaviour ology of absence seizures. The application of other of rats. Epilepsy Research, 1995; 21: 89–94. GABA-ergic drugs such as vigabatrin, an irreversible 13. Coenen, A. M. L., Dinkenburg, W. H. I. M., Inoue, M. et inhibitor of the GABA-transaminase, or baclofen, a al. Genetic models of absence epilepsy, with emphasis on the WAG/Rij strain of rats.
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