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Phenobarbital-induced atypical absence seizure in benign childhood epilepsy with centrotemporal spikes
Seizure 2002; 11: 201–204
doi:10.1053/seiz.2001.0568, available online at http://www.idealibrary.com on
CASE REPORT
Phenobarbital-induced atypical absence seizure in benign childhood epilepsy with centrotemporal spikes †
†
‡
SHIN-ICHIRO HAMANO , MIKA MOCHIZUKI & TAKEKI MORIKAWA †
Division of Neurology, Saitama Children’s Medical Center; Epilepsy Center, Shizuoka Higashi Hospital, Japan
‡ Department
of Pediatrics, National
Correspondence to: S. Hamano, MD, Division of Neurology, Saitama Children’s Medical Center, 2100 Magome, Iwatsuki, Saitama 339-8551, Japan. E-mail: [email protected]
This report describes atypical absence seizures induced by phenobarbital (PB) in a patient with benign childhood epilepsy with centrotemporal spikes. An 11-year-old girl had nocturnal motor seizures, beginning at the age of 7 years. Interictal EEG displayed centrotemporal sharp waves in the left and right sides alternatively, which increased significantly in frequency during sleep. She was given a diagnosis of benign childhood epilepsy with centrotemporal spike and was treated with valproic acid (VPA), which controlled her seizures for 3 years. She experienced nocturnal Rolandic seizures again, at the age of 10 years 2 months, 10 years 10 months in spite of the regular medication, and PB 60 mg daily was added to the VPA. Her parents noted de novo a few seconds of unresponsive fits 7 days after PB administration. Ictal EEG of the fits revealed diffuse irregular spike and wave bursts (1–4 seconds). VPA and PB in her blood was within the therapeutic ranges. After discontinuing PB, the atypical absence seizures immediately disappeared. Phenobarbital should be added to the list of drugs that potentially provoke de novo seizures. c 2002 BEA Trading Ltd. Published by Elsevier Science Ltd. All rights reserved
Key words: atypical absence seizure; benign childhood epilepsy with centrotemporal spike; pharmacodynamic drug interactions; phenobarbital; valproic acid.
INTRODUCTION
PATIENT REPORT
It is well known that some anticonvulsants may precipitate or exacerbate seizures although the serum concentration will be within the therapeutic range. Most of the reported cases with such adverse reaction were treated with carbamazepine or phenytoin. Phenobarbital (PB) is used widely in the world and has been used for a long time. Some cases have been reported to have involuntary movement induced by PB. Atypical absence seizures induced by PB have not been reported, according to our limited knowledge. This report describes atypical absence seizures provoked by PB in a patient with benign childhood epilepsy with centrotemporal spike (BECTS).
An 11-year-old girl had nocturnal motor seizures, including hemifacial spasms with drooling or hemiconvulsion, beginning at the age of 7 years. Her past medical history and family history were uneventful, and her developmental milestones were normal. Neurological examination and brain magnetic resonance imaging revealed no abnormality. Interictal EEG displayed centrotemporal sharp waves in the left and right sides alternatively, which increased significantly in frequency during sleep. She was given a diagnosis of BECTS and treated with valproic acid (VPA) 600 mg daily, which controlled her seizures well for 3 years. She experienced Rolandic seizures again, at
1059–1311/02/$22.00/0
c 2002 BEA Trading Ltd. Published by Elsevier Science Ltd. All rights reserved
202
S. Hamano et al.
Fig. 1: Electroencephalograms at the age of 11 years, including ictal record (awake). The dots indicate that centrotemporal sharp waves appeared in the left and right sides alternatively. The arrow shows the beginning of atypical absence seizures, which continued for a few seconds only accompanied with diffuse irregular sharp and wave bursts. As soon as the sharp and wave bursts ended, the patient could respond quickly to her name.
the age of 10 years 2 months, 10 years 10 months in spite of the regular medication, and PB 60 mg daily was added to the VPA. Her parents noted de novo a few seconds of unresponsive fits 7 days after PB was begun. These fits increased every few minutes in frequency while she was awake, and developed to being accompanied with head nodding or eye blinking one month later. Ictal EEG of the fits revealed diffuse irregular spike and wave bursts (1–4 seconds). Electromyogram of the bilateral trapezius showed no significant change (Figs 1 and 2). The alteration of muscle tone of the neck, trunk and extremities was obscure during the fits, for a short duration of the fits, except for the disappearance of artefacts of muscle activities which were superimposed bilaterally on Fp1 of figure. As soon as the spike and wave bursts ended, she could respond quickly to her name. We asked her to try to keep tapping a can with a pen regularly every second for 5 minutes. The rhythm of the tapping was delayed during the fits. The serum concentrations of VPA and PB was 56.0 and 15.6 µg ml−1 , respectively; both of them were within the therapeutic ranges. After the PB was discontinued, the atypical absence seizures immediately disappeared. VPA was increased up to
800 mg daily and then she experienced no seizure for the following 10 months.
DISCUSSION The rapid appearance of the atypical absences after adding PB, and also their rapid disappearance after discontinuing PB indicate that they were induced by PB; however, a repeat challenge with PB has not been performed. Carbamazepine and phenytoin have been the antiepileptic agents which most commonly induced or aggravated seizures, within or beyond the therapeutic ranges 1–4 . There have been several reports of PB-induced dyskinesia and interictal epileptic discharges 5 . No report was found that suggested that the seizures were induced or aggravated by using PB, except as an indirect side effect of sleepiness. This is the first report of PB-induced atypical absence seizures in BECTS within the therapeutic range. Seizures induced or aggravated by antiepileptic drugs should receive more attention. When a patient of BECTS suffers de novo absence seizures, atypical benign partial epilepsy might be diagnosed 6 . How-
Absence induced by phenobarbital
203
Fig. 2: Ictal electroencephalograms of another situation. The arrow shows the beginning of atypical absence seizures. Paroxysmal discharges in the right centro-midtemporal region preceded diffuse spike and wave. This electroencephalogram reveals marked irregularity of diffuse spike and wave and predominance in the right centro-midtemporal region.
ever, those seizures may include seizures induced or aggravated by antiepileptic drugs, even by PB. Misdiagnosis may lead to polypharmacy, instead of discontinuing the drug which probably induced the seizures. The mechanism by which PB produced atypical absence seizures in this patients is not clear. Benzodiazepines (BZDs) have been reported to exacerbate tonic status epilepticus in patients with Lennox– Gastaut syndrome and to induce microseizures in those with West syndrome 7–9 . Both BZDs and PB enhance postsynaptic γ -aminobutyric acid (GABA) receptor current by which rapid inhibition is mediated in the central nervous system, to provoke anticonvulsive effects 10, 11 . The duration of PB administration was only a short period in this patient; however, exacerbation of seizures by BZDs was reported in patients with chronic treatment of BZDs 8–10 . VPA, a concomitant medication in this patient, is thought to have two kinds of antiepileptic properties to intensify the release of GABA and to reduce sustained, high-frequency, repetitive firing of action potentials 10, 11 . The com-
bination of PB and VPA may modulate their effects on each other to induce atypical absence seizures in the patient. Whatever the mechanism is, this report indicates that the combination of PB and VPA in patient with BECTS may provoke de novo seizures. REFERENCES 1. Troupin, A. S. and Ojemann, L. M. Paradoxical intoxication– acomplication of anticonvulsant administration. Epilepsia 1975; 16: 753–758. 2. Shields, W. D. and Saslow, E. Myoclonic, atonic, and absence seizures following institution of carbamazepine therapy in children. Neurology 1983; 33: 1487–1489. 3. Lerman, P. Seizures induced or aggravated by anticonvulsants. Epilepsia 1986; 27: 706–710. 4. Osorio, I., Burnstine, T. H., Remler, B., Manon-Espaillat, R. and Reed, R. C. Phenytoin-induced seizures: a paradoxical effect at toxic concentrations in epileptic patients. Epilepsia 1989; 30: 230–234. 5. Sandyk, R. Phenobarbital-induced Tourette-like symptoms. Pediatric Neurology 1986; 2: 54–55. 6. Aicardi, J. and Chevrie, J. J. Atypical benign partial epilepsy of childhood. Developmental Medicine and Child Neurology 1982; 24: 281–292.
204 7. Tassinari, C. A., Dravet, C., Roger, J., Cano, J. P. and Gastaut, H. Tonic status epilepticus precipitated by intravenous benzodiazepine in five patients with Lennox–Gastaut syndrome. Epilepsia 1972; 13: 421–435. 8. Bittencourt, P. R.M. and Richens, A. Anticonvulsant induced status epilepticus in Lennox–Gastaut syndrome. Epilepsia 1981; 22: 129–134.
S. Hamano et al. 9. Otani, K., Tagawa, T., Futagi, Y., Okamoto, N. and Yabuuchi, M. Microseizures in west syndrome. Brain and Development 1991; 13: 196–199. 10. Macdonald, R. L. Antiepileptic drug actions. Epilepsia 1989; 30 (Suppl. 1): S19–S28. 11. Macdonald, R. L. and Kelly, K. M. Antiepileptic drug mechanisms of action. Epilepsia 1995; 36 (Suppl. 2): S2–S12.
doi:10.1053/seiz.2001.0568, available online at http://www.idealibrary.com on
CASE REPORT
Phenobarbital-induced atypical absence seizure in benign childhood epilepsy with centrotemporal spikes †
†
‡
SHIN-ICHIRO HAMANO , MIKA MOCHIZUKI & TAKEKI MORIKAWA †
Division of Neurology, Saitama Children’s Medical Center; Epilepsy Center, Shizuoka Higashi Hospital, Japan
‡ Department
of Pediatrics, National
Correspondence to: S. Hamano, MD, Division of Neurology, Saitama Children’s Medical Center, 2100 Magome, Iwatsuki, Saitama 339-8551, Japan. E-mail: [email protected]
This report describes atypical absence seizures induced by phenobarbital (PB) in a patient with benign childhood epilepsy with centrotemporal spikes. An 11-year-old girl had nocturnal motor seizures, beginning at the age of 7 years. Interictal EEG displayed centrotemporal sharp waves in the left and right sides alternatively, which increased significantly in frequency during sleep. She was given a diagnosis of benign childhood epilepsy with centrotemporal spike and was treated with valproic acid (VPA), which controlled her seizures for 3 years. She experienced nocturnal Rolandic seizures again, at the age of 10 years 2 months, 10 years 10 months in spite of the regular medication, and PB 60 mg daily was added to the VPA. Her parents noted de novo a few seconds of unresponsive fits 7 days after PB administration. Ictal EEG of the fits revealed diffuse irregular spike and wave bursts (1–4 seconds). VPA and PB in her blood was within the therapeutic ranges. After discontinuing PB, the atypical absence seizures immediately disappeared. Phenobarbital should be added to the list of drugs that potentially provoke de novo seizures. c 2002 BEA Trading Ltd. Published by Elsevier Science Ltd. All rights reserved
Key words: atypical absence seizure; benign childhood epilepsy with centrotemporal spike; pharmacodynamic drug interactions; phenobarbital; valproic acid.
INTRODUCTION
PATIENT REPORT
It is well known that some anticonvulsants may precipitate or exacerbate seizures although the serum concentration will be within the therapeutic range. Most of the reported cases with such adverse reaction were treated with carbamazepine or phenytoin. Phenobarbital (PB) is used widely in the world and has been used for a long time. Some cases have been reported to have involuntary movement induced by PB. Atypical absence seizures induced by PB have not been reported, according to our limited knowledge. This report describes atypical absence seizures provoked by PB in a patient with benign childhood epilepsy with centrotemporal spike (BECTS).
An 11-year-old girl had nocturnal motor seizures, including hemifacial spasms with drooling or hemiconvulsion, beginning at the age of 7 years. Her past medical history and family history were uneventful, and her developmental milestones were normal. Neurological examination and brain magnetic resonance imaging revealed no abnormality. Interictal EEG displayed centrotemporal sharp waves in the left and right sides alternatively, which increased significantly in frequency during sleep. She was given a diagnosis of BECTS and treated with valproic acid (VPA) 600 mg daily, which controlled her seizures well for 3 years. She experienced Rolandic seizures again, at
1059–1311/02/$22.00/0
c 2002 BEA Trading Ltd. Published by Elsevier Science Ltd. All rights reserved
202
S. Hamano et al.
Fig. 1: Electroencephalograms at the age of 11 years, including ictal record (awake). The dots indicate that centrotemporal sharp waves appeared in the left and right sides alternatively. The arrow shows the beginning of atypical absence seizures, which continued for a few seconds only accompanied with diffuse irregular sharp and wave bursts. As soon as the sharp and wave bursts ended, the patient could respond quickly to her name.
the age of 10 years 2 months, 10 years 10 months in spite of the regular medication, and PB 60 mg daily was added to the VPA. Her parents noted de novo a few seconds of unresponsive fits 7 days after PB was begun. These fits increased every few minutes in frequency while she was awake, and developed to being accompanied with head nodding or eye blinking one month later. Ictal EEG of the fits revealed diffuse irregular spike and wave bursts (1–4 seconds). Electromyogram of the bilateral trapezius showed no significant change (Figs 1 and 2). The alteration of muscle tone of the neck, trunk and extremities was obscure during the fits, for a short duration of the fits, except for the disappearance of artefacts of muscle activities which were superimposed bilaterally on Fp1 of figure. As soon as the spike and wave bursts ended, she could respond quickly to her name. We asked her to try to keep tapping a can with a pen regularly every second for 5 minutes. The rhythm of the tapping was delayed during the fits. The serum concentrations of VPA and PB was 56.0 and 15.6 µg ml−1 , respectively; both of them were within the therapeutic ranges. After the PB was discontinued, the atypical absence seizures immediately disappeared. VPA was increased up to
800 mg daily and then she experienced no seizure for the following 10 months.
DISCUSSION The rapid appearance of the atypical absences after adding PB, and also their rapid disappearance after discontinuing PB indicate that they were induced by PB; however, a repeat challenge with PB has not been performed. Carbamazepine and phenytoin have been the antiepileptic agents which most commonly induced or aggravated seizures, within or beyond the therapeutic ranges 1–4 . There have been several reports of PB-induced dyskinesia and interictal epileptic discharges 5 . No report was found that suggested that the seizures were induced or aggravated by using PB, except as an indirect side effect of sleepiness. This is the first report of PB-induced atypical absence seizures in BECTS within the therapeutic range. Seizures induced or aggravated by antiepileptic drugs should receive more attention. When a patient of BECTS suffers de novo absence seizures, atypical benign partial epilepsy might be diagnosed 6 . How-
Absence induced by phenobarbital
203
Fig. 2: Ictal electroencephalograms of another situation. The arrow shows the beginning of atypical absence seizures. Paroxysmal discharges in the right centro-midtemporal region preceded diffuse spike and wave. This electroencephalogram reveals marked irregularity of diffuse spike and wave and predominance in the right centro-midtemporal region.
ever, those seizures may include seizures induced or aggravated by antiepileptic drugs, even by PB. Misdiagnosis may lead to polypharmacy, instead of discontinuing the drug which probably induced the seizures. The mechanism by which PB produced atypical absence seizures in this patients is not clear. Benzodiazepines (BZDs) have been reported to exacerbate tonic status epilepticus in patients with Lennox– Gastaut syndrome and to induce microseizures in those with West syndrome 7–9 . Both BZDs and PB enhance postsynaptic γ -aminobutyric acid (GABA) receptor current by which rapid inhibition is mediated in the central nervous system, to provoke anticonvulsive effects 10, 11 . The duration of PB administration was only a short period in this patient; however, exacerbation of seizures by BZDs was reported in patients with chronic treatment of BZDs 8–10 . VPA, a concomitant medication in this patient, is thought to have two kinds of antiepileptic properties to intensify the release of GABA and to reduce sustained, high-frequency, repetitive firing of action potentials 10, 11 . The com-
bination of PB and VPA may modulate their effects on each other to induce atypical absence seizures in the patient. Whatever the mechanism is, this report indicates that the combination of PB and VPA in patient with BECTS may provoke de novo seizures. REFERENCES 1. Troupin, A. S. and Ojemann, L. M. Paradoxical intoxication– acomplication of anticonvulsant administration. Epilepsia 1975; 16: 753–758. 2. Shields, W. D. and Saslow, E. Myoclonic, atonic, and absence seizures following institution of carbamazepine therapy in children. Neurology 1983; 33: 1487–1489. 3. Lerman, P. Seizures induced or aggravated by anticonvulsants. Epilepsia 1986; 27: 706–710. 4. Osorio, I., Burnstine, T. H., Remler, B., Manon-Espaillat, R. and Reed, R. C. Phenytoin-induced seizures: a paradoxical effect at toxic concentrations in epileptic patients. Epilepsia 1989; 30: 230–234. 5. Sandyk, R. Phenobarbital-induced Tourette-like symptoms. Pediatric Neurology 1986; 2: 54–55. 6. Aicardi, J. and Chevrie, J. J. Atypical benign partial epilepsy of childhood. Developmental Medicine and Child Neurology 1982; 24: 281–292.
204 7. Tassinari, C. A., Dravet, C., Roger, J., Cano, J. P. and Gastaut, H. Tonic status epilepticus precipitated by intravenous benzodiazepine in five patients with Lennox–Gastaut syndrome. Epilepsia 1972; 13: 421–435. 8. Bittencourt, P. R.M. and Richens, A. Anticonvulsant induced status epilepticus in Lennox–Gastaut syndrome. Epilepsia 1981; 22: 129–134.
S. Hamano et al. 9. Otani, K., Tagawa, T., Futagi, Y., Okamoto, N. and Yabuuchi, M. Microseizures in west syndrome. Brain and Development 1991; 13: 196–199. 10. Macdonald, R. L. Antiepileptic drug actions. Epilepsia 1989; 30 (Suppl. 1): S19–S28. 11. Macdonald, R. L. and Kelly, K. M. Antiepileptic drug mechanisms of action. Epilepsia 1995; 36 (Suppl. 2): S2–S12.