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Forced normalization: An overlooked entity in epileptic patients
Asian Journal of Psychiatry 23 (2016) 93–94
Contents lists available at ScienceDirect
Asian Journal of Psychiatry journal homepage: www.elsevier.com/locate/ajp
Short communication
Forced normalization: An overlooked entity in epileptic patients Andac Topkan, MD., Sule Bilen, MD.* , Ayse Pinar Titiz, MD., Esra Eruyar, MD., Fikri Ak, MD. Neurology Department of Ankara Numune Training and Research Hospital, Turkey
A R T I C L E I N F O
Article history: Received 6 July 2016 Received in revised form 22 July 2016 Accepted 23 July 2016 Available online xxx Keywords: Epilepsy Forced normalization Normal EEG Psychosis
A B S T R A C T
The “forced normalization” phenomenon is characterized by acute/subacute onset of psychotic symptoms in the early post-ictal period with dramatic improvement of electrophysiological epileptiform activity. A 56 years old female with going on personality changes, maladaptive behaviours and a mild cognitive impairment since last seizure which was forty-five days ago has been admitted. An evident increase was observed in her maladaptive behaviours with the use of levetiracetam. She began describing visual hallucinations and déjàvu. Control EEG performed 24 h after the seizure was completely normal. Levetiracetam therapy was replaced with phenytoin. Quetiapine therapy was also administered. Psychotic symptoms disappeared. ã 2016 Elsevier B.V. All rights reserved.
1. Introduction There is a growing interest in the relationship between epilepsy and psychosis since it has been introduced 150 years ago. Despite there are many common features, some differences between postictal psychosis and “forced normalization” phenomenon are described in clinical and electrophysiological aspects (Nadkarni et al., 2007). Here we report an epileptic patient who has been diagnosed as forced normalization according to her history, clinical and electrophysiological findings. 2. Case report A 56 years old female patient with a history of three epileptic seizures in a period of 16 months’ was admitted to the neurology clinic. Her family members were describing personality changes, maladaptive behaviours and a mild cognitive decline beginning with the last seizure forty-five days ago. She had a two minutes long, secondary generalized tonic clonic seizure during hospitalization. Her post-ictal EEG showed bilateral parietotempora l epileptiform paroxysmal activity (Fig. 1). Levetiracetam 1000 mg/ day was added to her therapy. Following a 12 h of post-ictal confusion period she had an evident increase in her maladaptive behaviours. Additionally she began describing visual
* Corresponding author at: Ankara Numune Hastanesi NorolojiKlinigi, Talatpasa Bulvari, No.5, Samanpazari/Ankara/Turkey. Postal code: 06100. E-mail addresses: [email protected] (A. Topkan), [email protected] (S. Bilen), [email protected] (A.P. Titiz), [email protected] (E. Eruyar), fi[email protected] (F. Ak). http://dx.doi.org/10.1016/j.ajp.2016.07.017 1876-2018/ã 2016 Elsevier B.V. All rights reserved.
hallucinations and déjàvu. Her control EEG was evaluated as completely normal (Fig. 2) in this period of time. Levetiracetam therapy was replaced with phenytoin 300 mg/day. Quetiapine 50 mg/day therapy was also administered. Psychotic symptoms completely disappeared in two weeks. During her follow-up she was free of epileptic seizures under phenytoin treatment. Quetiapine therapy was stopped in a few weeks. 3. Discussion There is a complex relationship between epilepsy and psychosis. Psychosis is 6–12 times more prevalent among epileptic patients compared to general population. Data about the epilepsy prevalence in psychotic patients are contradictory (Toone, 2000; Cascella et al., 2009). On the other hand electro convulsive therapy, an effective treatment modality for psychosis reveals a possible antagonism between epileptic seizures and psychosis (Loganathan et al., 2015). Post-ictal psychosis occurs mostly following complex partial seizures within the 12 h to 7 days. It is described as a benign entity that is responsive to low dose antipsychotic therapy. The “forced normalization” phenomenon which was introduced in 1958 can easily be confused with post-ictal psychosis (Sachdev, 1998). Forced normalization is described as acute/subacute onset of psychotic symptoms accompanying to clinically successful seizure control and dramatic improvement of epileptiform activity in the EEG in post-ictal period. Sometimes this picture coexists with addition of a new antiepileptic agent (Loganathan et al., 2015; Roy et al., 2014). Positive psychotic symptoms occur predominantly. Distrupted inhibitor activity of cerebral cortex on limbic system following seizure control is blamed in the pathophysiology
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A. Topkan et al. / Asian Journal of PsychiatryAJP 23 (2016) 93–94
(Pollock, 1987). Some authors claim that, repetetive stimulation of limbic system originating from amygdala which is called “limbic kindling” causes behaviour changes (Loganathan et al., 2015; Weber et al., 2012). Some antiepileptic agents but mostly ethosuximide, vigabatrine, and topiramate are also considered as responsible for this picture. Thus forced normalization, might be conceived as a side effect of recently administered antiepileptic agent (Anzellotti et al., 2014). We evaluated the behavioural changes, hallucinations with simultaneous EEG improvement of our patient as forced normalization and we observed an evident increase of abnormal behaviours with the use of levetiracetam. We hypothesized that such a clinical picture occured as a result of fast titration of levetiracetam. Levetiracetam is reported rarely as causing to forced normalization compared to some other antiepileptic agents. Since many antiepileptic drugs with different mechanisms of action are related to forced normalization, predicting this clinical picture seems impossible. Conflict of interest There is no conflict of interest. Funding Fig. 1. Bilateral synchronous, symmetrical sharp and slow waves interfering with cerebral bioelectrical activity especially in pariatotemporal regions.
There is no funding to declare. References Anzellotti, F., Franciotti, R., Zhuzhuni, H., et al., 2014. Nonepileptic seizures under levetiracetam therapy: a case report of forced normalization process. Neuropsychiatr. Dis Treat. 23 (10), 959–964. Cascella, N.G., Schretlen, D.J., Sawa, A., 2009. Schizophrenia and epilepsy: is there a shared susceptibility? NeurosciRes 63 (4), 227–235. Loganathan, M.A., Enja, M., Lippmann, S., 2015. Forced normalization: epilepsy and psychosis interaction. Innov. Clin. Neurosci. 12 (5–6), 38–41. Nadkarni, S., Arnedo, V., Devinsky, O., 2007. Psychosis in epilepsypatients. Epilepsia 48 (Suppl. 9), 17–19. Pollock, D.C., 1987. Models for understanding the antagonism between seizures and psychosis. Prog. Neuropsychopharmacol. Biol. Psychiatry 11 (4), 483–504. Roy, K., Balon, R., Penumetcha, V., Levine, B.H., 2014. Psychosis and seizure disorder: challenges in diagnosis and treatment. Curr. Psychiatry Rep. 16 (11), 509. Sachdev, P., 1998. Schizophrenia-like psychosis and epilepsy: the status of the association. Am. J. Psychiatry 155 (3), 325–336. Toone, B.K., 2000. The psychoses of epilepsy. J. Neurol. Neurosurg. Psychiatry 69, 1–– 3. Weber, P., Dill, P., Datta, A.N., 2012. Vigabatrin-induced forced normalization and psychosis—prolongated termination of behavioral symptoms but persistent antiepileptic effect after withdrawal. Epilepsy Behav. 24 (1), 138–140.
Fig. 2. Normal EEG with pariatooccipital alpha rythm.
Contents lists available at ScienceDirect
Asian Journal of Psychiatry journal homepage: www.elsevier.com/locate/ajp
Short communication
Forced normalization: An overlooked entity in epileptic patients Andac Topkan, MD., Sule Bilen, MD.* , Ayse Pinar Titiz, MD., Esra Eruyar, MD., Fikri Ak, MD. Neurology Department of Ankara Numune Training and Research Hospital, Turkey
A R T I C L E I N F O
Article history: Received 6 July 2016 Received in revised form 22 July 2016 Accepted 23 July 2016 Available online xxx Keywords: Epilepsy Forced normalization Normal EEG Psychosis
A B S T R A C T
The “forced normalization” phenomenon is characterized by acute/subacute onset of psychotic symptoms in the early post-ictal period with dramatic improvement of electrophysiological epileptiform activity. A 56 years old female with going on personality changes, maladaptive behaviours and a mild cognitive impairment since last seizure which was forty-five days ago has been admitted. An evident increase was observed in her maladaptive behaviours with the use of levetiracetam. She began describing visual hallucinations and déjàvu. Control EEG performed 24 h after the seizure was completely normal. Levetiracetam therapy was replaced with phenytoin. Quetiapine therapy was also administered. Psychotic symptoms disappeared. ã 2016 Elsevier B.V. All rights reserved.
1. Introduction There is a growing interest in the relationship between epilepsy and psychosis since it has been introduced 150 years ago. Despite there are many common features, some differences between postictal psychosis and “forced normalization” phenomenon are described in clinical and electrophysiological aspects (Nadkarni et al., 2007). Here we report an epileptic patient who has been diagnosed as forced normalization according to her history, clinical and electrophysiological findings. 2. Case report A 56 years old female patient with a history of three epileptic seizures in a period of 16 months’ was admitted to the neurology clinic. Her family members were describing personality changes, maladaptive behaviours and a mild cognitive decline beginning with the last seizure forty-five days ago. She had a two minutes long, secondary generalized tonic clonic seizure during hospitalization. Her post-ictal EEG showed bilateral parietotempora l epileptiform paroxysmal activity (Fig. 1). Levetiracetam 1000 mg/ day was added to her therapy. Following a 12 h of post-ictal confusion period she had an evident increase in her maladaptive behaviours. Additionally she began describing visual
* Corresponding author at: Ankara Numune Hastanesi NorolojiKlinigi, Talatpasa Bulvari, No.5, Samanpazari/Ankara/Turkey. Postal code: 06100. E-mail addresses: [email protected] (A. Topkan), [email protected] (S. Bilen), [email protected] (A.P. Titiz), [email protected] (E. Eruyar), fi[email protected] (F. Ak). http://dx.doi.org/10.1016/j.ajp.2016.07.017 1876-2018/ã 2016 Elsevier B.V. All rights reserved.
hallucinations and déjàvu. Her control EEG was evaluated as completely normal (Fig. 2) in this period of time. Levetiracetam therapy was replaced with phenytoin 300 mg/day. Quetiapine 50 mg/day therapy was also administered. Psychotic symptoms completely disappeared in two weeks. During her follow-up she was free of epileptic seizures under phenytoin treatment. Quetiapine therapy was stopped in a few weeks. 3. Discussion There is a complex relationship between epilepsy and psychosis. Psychosis is 6–12 times more prevalent among epileptic patients compared to general population. Data about the epilepsy prevalence in psychotic patients are contradictory (Toone, 2000; Cascella et al., 2009). On the other hand electro convulsive therapy, an effective treatment modality for psychosis reveals a possible antagonism between epileptic seizures and psychosis (Loganathan et al., 2015). Post-ictal psychosis occurs mostly following complex partial seizures within the 12 h to 7 days. It is described as a benign entity that is responsive to low dose antipsychotic therapy. The “forced normalization” phenomenon which was introduced in 1958 can easily be confused with post-ictal psychosis (Sachdev, 1998). Forced normalization is described as acute/subacute onset of psychotic symptoms accompanying to clinically successful seizure control and dramatic improvement of epileptiform activity in the EEG in post-ictal period. Sometimes this picture coexists with addition of a new antiepileptic agent (Loganathan et al., 2015; Roy et al., 2014). Positive psychotic symptoms occur predominantly. Distrupted inhibitor activity of cerebral cortex on limbic system following seizure control is blamed in the pathophysiology
94
A. Topkan et al. / Asian Journal of PsychiatryAJP 23 (2016) 93–94
(Pollock, 1987). Some authors claim that, repetetive stimulation of limbic system originating from amygdala which is called “limbic kindling” causes behaviour changes (Loganathan et al., 2015; Weber et al., 2012). Some antiepileptic agents but mostly ethosuximide, vigabatrine, and topiramate are also considered as responsible for this picture. Thus forced normalization, might be conceived as a side effect of recently administered antiepileptic agent (Anzellotti et al., 2014). We evaluated the behavioural changes, hallucinations with simultaneous EEG improvement of our patient as forced normalization and we observed an evident increase of abnormal behaviours with the use of levetiracetam. We hypothesized that such a clinical picture occured as a result of fast titration of levetiracetam. Levetiracetam is reported rarely as causing to forced normalization compared to some other antiepileptic agents. Since many antiepileptic drugs with different mechanisms of action are related to forced normalization, predicting this clinical picture seems impossible. Conflict of interest There is no conflict of interest. Funding Fig. 1. Bilateral synchronous, symmetrical sharp and slow waves interfering with cerebral bioelectrical activity especially in pariatotemporal regions.
There is no funding to declare. References Anzellotti, F., Franciotti, R., Zhuzhuni, H., et al., 2014. Nonepileptic seizures under levetiracetam therapy: a case report of forced normalization process. Neuropsychiatr. Dis Treat. 23 (10), 959–964. Cascella, N.G., Schretlen, D.J., Sawa, A., 2009. Schizophrenia and epilepsy: is there a shared susceptibility? NeurosciRes 63 (4), 227–235. Loganathan, M.A., Enja, M., Lippmann, S., 2015. Forced normalization: epilepsy and psychosis interaction. Innov. Clin. Neurosci. 12 (5–6), 38–41. Nadkarni, S., Arnedo, V., Devinsky, O., 2007. Psychosis in epilepsypatients. Epilepsia 48 (Suppl. 9), 17–19. Pollock, D.C., 1987. Models for understanding the antagonism between seizures and psychosis. Prog. Neuropsychopharmacol. Biol. Psychiatry 11 (4), 483–504. Roy, K., Balon, R., Penumetcha, V., Levine, B.H., 2014. Psychosis and seizure disorder: challenges in diagnosis and treatment. Curr. Psychiatry Rep. 16 (11), 509. Sachdev, P., 1998. Schizophrenia-like psychosis and epilepsy: the status of the association. Am. J. Psychiatry 155 (3), 325–336. Toone, B.K., 2000. The psychoses of epilepsy. J. Neurol. Neurosurg. Psychiatry 69, 1–– 3. Weber, P., Dill, P., Datta, A.N., 2012. Vigabatrin-induced forced normalization and psychosis—prolongated termination of behavioral symptoms but persistent antiepileptic effect after withdrawal. Epilepsy Behav. 24 (1), 138–140.
Fig. 2. Normal EEG with pariatooccipital alpha rythm.