Epilepsy & Behavior 23 (2012) 426–430
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Postictal psychosis and its electrophysiological correlates in invasive EEG: A case report study and literature review Robert Kuba ⁎, Milan Brázdil, Ivan Rektor Brno Epilepsy Centre, First Department of Neurology, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic
a r t i c l e
i n f o
Article history: Received 4 January 2012 Revised 4 February 2012 Accepted 5 February 2012 Available online 20 March 2012 Keywords: Psychosis Postictal Epilepsy Temporal Invasive EEG
a b s t r a c t We identiﬁed two patients with medically refractory temporal lobe epilepsy, from whom intracranial EEG recordings were obtained at the time of postictal psychosis. Both patients had mesial temporal epilepsy associated with hippocampal sclerosis. In both patients, the postictal psychosis was associated with a continual “epileptiform” EEG pattern that differed from their interictal and ictal EEG ﬁndings (rhythmical slow wave and “abortive” spike-slow wave complex activity in the right hippocampus and lateral temporal cortex in case 1 and a periodic pattern of triphasic waves in the contacts recording activity from the left anterior cingulate gyrus). Some cases of postictal psychosis might be caused by the transient impairment of several limbic system structures due to the “continual epileptiform discharge” in some brain regions. Case 2 is the ﬁrst report of a patient with TLE in whom psychotic symptoms were associated with the epileptiform impairment of the anterior cingulate gyrus. © 2012 Elsevier Inc. All rights reserved.
1. Introduction Postictal psychosis (PP) is one of the most common types of psychosis in patients suffering from epilepsy. It comprises about 25% of all psychoses in epilepsy patients . Postictal psychosis usually develops after a cluster of generalized tonic-clonic seizures (GTCS) or focal seizures. The incidence of PP ranges widely. The most precise data are available in epilepsy monitoring units, where PP affects about 6 to 10% of all presurgical candidates [2,3]. Clinically, PP is typically characterized by hallucinations, delusions, affective change, and aggression . In general, diagnostic criteria by Logsdail and Toone are applied for the diagnosis of PP . The pathogenesis of PP is not fully understood. It is more often present in focal epilepsy, especially temporal lobe epilepsy (TLE) [3,5,6] and in patients with diffuse CNS injury and bilateral EEG abnormalities [7,8]. Several single-photon emission computed tomography (SPECT) studies showed the hyperactivation of various regions in both the frontal and temporal lobes [9–12]. There are only a few case reports of patients with PP in whom PP was present during an invasive EEG recording. In some of them, PP was associated with continual epileptiform discharge, mostly either in the mesial or lateral temporal lobe structures [13–16]. In others, the invasive EEG from these structures was negative [17,18].
⁎ Corresponding author at: Brno Epilepsy Centre, First Department of Neurology, St. Anne's University Hospital and Faculty of Medicine, Masaryk University Brno, Pekařská 53, 656 91 Brno, Czech Republic. Fax: + 420 543 182 624. E-mail address: [email protected]
(R. Kuba). 1525-5050/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2012.02.004
We describe two patients with refractory mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) who were preoperatively evaluated using depth electrodes. In both patients, PP developed during intracranial EEG recording after a cluster of seizures. We analyze the course of invasive EEG ﬁndings and their relation to symptoms of PP in these patients. 2. Methods 2.1. Representative case report 1 The ﬁrst patient was a 32-year-old, right-handed man with rightsided MTLE associated with HS. He had febrile seizures at 8 months of age, and focal epilepsy developed when he was 17 years old. His seizures usually started with epigastric sensations rising to the head, followed by loss of consciousness with oroalimentary and limb automatisms. The epilepsy was refractory to all antiepileptic drugs he received (in total 8 antiepileptic drugs). Magnetic resonance imaging (MRI) showed HS on the right; interictal FDG-positron emission tomography (FDG-PET) revealed large hypometabolism of the right temporal lobe. Scalp video-EEG showed bitemporal interictal epileptiform discharges over both the right and left temporal and sphenoidal electrodes. Ictal EEG was non-conclusive, with delayed bitemporal rhythmic slow activity. For this reason, the patient underwent invasive EEG monitoring with depth electrodes in 2002. Five electrodes (A, B, C, D, and T) were implanted at the right temporal lobe orthogonally and one oblique electrode (X′) targeted to the left amygdalohippocampal complex (AHC) (Fig. 1A). The invasive monitoring lasted 7 days. During the ﬁrst 4 days, antiepileptic medication was
R. Kuba et al. / Epilepsy & Behavior 23 (2012) 426–430
Fig. 1. Case 1. A. Localization of intracerebral contacts: Electrodes on the right side: A — mesial amygdala, lateral middle temporal gyrus; B — mesial anterior hippocampus, lateral middle temporal gyrus; C — mesial posterior hippocampus, lateral middle temporal gyrus; D — posterior part of medial temporal gyrus; T — temporal operculum). Electrode on the left side: X' — mesial amygdalo-hippocampal complex. B. Interictal ﬁndings: Spikes and spike-wave complexes in C 1, 2 (hippocampus on the right side). C. Ictal ﬁndings: The development of fast epileptic activity in C 1–5 and A1, 2 (hippocampus on the right side).
completely withdrawn (the patient had been on a stable dose of lamotrigine 400 mg/day and carbamazepine 1200 mg/day). On the ﬁfth day in the morning, two complex partial seizures occurred, both arising from the right hippocampus (Figs. 1B,C). On the same day in the afternoon, a cluster of six more seizures occurred. The patient was returned to his chronic medication and was administered 5 mg of midazolam intravenously. During the night, about 10 h after the cluster of focal seizures, the patient became restless, experiencing both visual and auditory hallucinations and delusions of persecution. He was treated with a combination of intravenous midazolam and haloperidol. The psychotic symptoms disappeared in about 15 h. For the full duration of the psychotic symptoms, the invasive EEG showed a uniform pattern of rhythmic slow waves and “abortive” spike-wave complexes (SWC) in the right hippocampus and in the right temporal neocortex (Fig. 2). This pattern differed from both the interictal and ictal EEG of the patient, and it was stable during the whole period of postictal psychosis and disappeared in relation to the cessation of
Fig. 2. EEG during psychotic symptoms in case 1: continual rhythmic delta (1- to 2-Hz) or abortive SWC in the right hippocampus and lateral temporal cortex (contacts B1, B2, B3, B5, C1, C2 C3, C5) (indicated by arrow).
psychotic symptoms. The patient underwent right antero-mesial temporal lobe resection and is now completely seizure-free and off antiepileptic treatment.
2.2. Representative case report 2 The second patient was a 40-year-old, right-handed man with left-sided MTLE associated with HS. He had viral encephalitis at 4 years of age, and focal epilepsy developed when he was 8 years old. His seizures started usually with “déjà vu” or “déjà vecu” illusions, followed by loss of consciousness with oroalimentary and limb automatisms. The epilepsy was refractory to all antiepileptic drugs he received (in total 10 antiepileptic drugs). MRI showed HS on the left; interictal FDG-PET revealed bitemporal hypometabolism more accentuated on the left. Scalp video-EEG showed bitemporal interictal epileptiform discharges over both the right and left temporal and sphenoidal electrodes. Ictal EEG was non-conclusive, with delayed bitemporal rhythmic slow activity accentuated on the right. For this reason, the patient underwent invasive EEG monitoring with depth electrodes in 2008. Six orthogonal electrodes were implanted on the right (A, B, C, G, O, and Fo) and 6 electrodes on the left (A′, B′, C′, G′, O′, and Fo′) (Fig. 3A). The invasive monitoring lasted 7 days. After complete drug withdrawal (the patient was on a stable dose of levetiracetam 2500 mg/day and carbamazepine 1000 mg/day), 5 seizures were recorded; 2 of which became secondarily generalized. All seizures arose from the left hippocampus (Figs. 3B,C) and spread to the right temporal lobe structures. On the ﬁfth day of monitoring, the patient became restless 5 h after the last seizure, becoming aggressive and experiencing auditory hallucinations (his father's voice told him to leave the hospital). The patient was treated with a combination of intravenous midazolam and olanzapine. The psychotic symptoms disappeared in about 10 h. The invasive EEG showed a uniform pattern of periodic triphasic waves in the left anterior cingulate gyrus (ACG) for the duration of the psychotic symptoms (Fig. 4). This pattern was different from both the interictal and ictal EEGs of the patient. This pattern was continual during the whole period of psychiatric symptoms and disappeared in relation to the cessation of symptoms. On the last day of the invasive monitoring, the patient was stimulated, eliciting focal seizures from both the left and right mesiotemporal structures. The patient underwent a left
R. Kuba et al. / Epilepsy & Behavior 23 (2012) 426–430
Fig. 3. Case 2. A. Localization of intracerebral contacts: Electrodes on the left side: A' — mesial amygdala, lateral middle temporal gyrus; B' — mesial anterior hippocampus, lateral middle temporal gyrus; C' — mesial posterior hippocampus, lateral middle temporal gyrus; O' — orbitofrontal cortex; G' — mesial anterior cingulate gyrus, lateral middle frontal gyrus; Fo' — frontal operculum). Electrodes on the left side: A — mesial amygdala, lateral middle temporal gyrus; B — mesial anterior hippocampus, lateral middle temporal gyrus; C — mesial posterior hippocampus, lateral middle temporal gyrus; O — orbitofrontal cortex; G — mesial anterior cingulate gyrus, lateral middle frontal gyrus; Fo — frontal operculum). B. Interictal ﬁndings: Spikes and spike-wave complexes in C' 1, 2 (hippocampus on the left side) and B 1–5 (hippocampus on the right side). The ﬁnding on the left side is more active. C. Ictal ﬁndings: The development of fast epileptic activity in C'1–5 (hippocampus on the left side).
antero-mesial temporal lobe resection and his outcome is now classiﬁed as Engel IIIA. 3. Discussion We described 2 cases with MTLE in whom PP, as deﬁned by the traditional criteria of Logsdail and Toone , occurred during intracranial EEG monitoring. The duration of psychiatric symptoms was shortened, probably because of the aggressive treatment of both cases with a combination of intravenously administered benzodiazepines and neuroleptics. In both cases, PP developed after a complete
drug withdrawal followed by a cluster of epileptic seizures. In both cases, the psychiatric symptoms occurred several hours after a seizure cluster. In both patients, the PP was associated with a continual EEG pattern that differed from both the interictal and ictal EEG patterns typical for each patient. This EEG pattern appeared and disappeared in relation to the appearance and disappearance of psychiatric symptoms. The pattern consisted of rhythmic slow waves and abortive SWC in both right mesial and lateral temporal lobe structures (case 1), and of periodic triphasic waves in the left anterior cingulate gyrus (case 2). In both cases, it was located ipsilaterally to the proven seizure onset zone.
Fig. 4. EEG during psychotic symptoms in case 2: continual periodic triphasic wave pattern in the left anterior cingulate gyrus (contacts G′1, G′2) (indicated by arrow).
R. Kuba et al. / Epilepsy & Behavior 23 (2012) 426–430
To our knowledge, there are only a few literature reports in which invasive EEG recording was available during psychotic symptoms in patients with epilepsy (Table 1). Takeda et al.  described a 25-year-old woman with MTLE associated with a slight hyperintensity of the left hippocampus in MRI (T2 and FLAIR images). The patient underwent invasive EEG with combined depth and subdural electrodes. All seizures arose from the left mesiotemporal region. Two days after a cluster of seizures, PP developed. It clinically presented as stupor, auditory hallucinations, and fear. The EEG during the PP showed rhythmic spike-slow wave discharges restricted to the left amygdala. The discharges diminished in association with the improvement of psychiatric symptoms. Kanemoto  reported a 24-year-old woman with MTLE associated with hippocampal sclerosis. In addition to focal seizures, the patient presented with episodes of “Capgras syndrome” lasting several hours. She felt that friends and relatives had become completely different persons overnight, replaced by impostors. The patient was investigated with depth electrodes. Focal seizures started from the left mesiotemporal region. The psychotic symptoms were associated with a rhythmic epileptic discharge in the left mesiotemporal region. The EEG patterns associated with psychotic symptoms in both of the cited reports were rhythmic and regular, resembling the ictal discharge [14,16]. For this reason, the psychosis in these cases should be considered ictal rather than postictal. Two other reports demonstrated EEG patterns that were different from the ictal EEG in the presented patients. So et al. reported a 19year-old man with left TLE who developed PP during intracranial monitoring using both depth and epidural electrodes. Clinically, the PP presented as auditory hallucinations and paranoid delusion. EEG showed very frequent interictal epileptiform discharges bitemporally, maximally involving the mesiotemporal structures . Seeck et al.  presented a case of a 20-year-old woman with refractory multifocal epilepsy due to meningoencephalitis. Magnetic resonance imaging did not reveal any lesion, and functional neuroimaging investigation showed the multifocal involvement of temporal and frontal lobes. Depth electrodes were used to reveal the seizure onset zone. After 9 days of monitoring, the patient experienced a psychotic episode with mystic delusions and auditory hallucinations. The correlate of these psychotic symptoms was a continual pattern of semirhythmical sharp slow waves in the left anterior neocortical region (accompanied by an increase in known lateral temporal spikes). This pattern had never presented before in the patient's EEG. On the other hand, Mathern et al.  reported a patient with TLE who died after epilepsy surgery. The PP in this patient was not associated with any change of interictal EEG during the psychotic symptoms. Most recently, Schulze-Bonhage and van Elst reported two patients with TLE who developed PP during intracranial monitoring after seizure clustering. In evaluating the temporal lobe regions of both patients, it appeared that the development of PP was not related to any subclinical epileptiform activity . Our cases with PP more closely resemble the patients presented by So et al. and Seeck et al. [13,15]. The EEG pattern associated with
psychotic symptoms differed from each patient's ictal EEG during habitual seizures. To our knowledge, our case 2 is the ﬁrst case of a patient with TLE in whom invasive EEG revealed a continual EEG change in ACG, while the temporal lobe seems to remain intact during a psychotic period. In the contacts recording activity from the left ACG, the continual periodic discharge of triphasic waves occurred and lasted during the whole period of PP. The possible impairment of ACG in the genesis of schizophrenia and other psychotic disorders has been demonstrated in several studies. For example, Buchsbaum et al. , using FDG-PET in various cortical and subcortical structures including the cingulate gyrus, demonstrated signiﬁcantly lower relative glucose metabolism in patients suffering from schizophrenia in comparison to healthy volunteers. Another recently published functional imaging study using diffusion tensor imaging (DTI) showed white matter abnormalities in several brain regions including the left ACG in patients with schizophrenia and other schizoaffective disorders. These abnormalities were associated with symptom unawareness . These ﬁndings support the hypothesis that transient impairment of the ACG may contribute to the development of psychotic symptoms in patients with epilepsy during the postictal period. Several functional neuroimaging studies showed hyperperfusion in various cerebral regions during PP. Fong et al. demonstrated two patients with right TLE in whom the PP was associated with regional hyperperfusion in the right temporal lobe and left basal ganglia on SPECT performed during PP . Adding another four patients (2 with TLE, 2 with GTCS), they demonstrated that the hyperperfusion on the SPECT was located mostly over the lateral temporal neocortical regions . Nishida et al. demonstrated hyperperfusion and other functional changes during PP in both the frontal and temporal lobes (mostly on the right side), including the operculoinsular cortex and cingulate gyrus in one patient with frontal lobe epilepsy . Hyperactivation of both temporal and frontal lobes during PP was also revealed by another study evaluating 5 patients suffering from TLE . These results suggest that PP is a result of excessive activation of particular cerebral structures rather than a “deactivation” during the postictal depression caused by a cluster of focal or generalized seizures. Thus, PP might be a “rebound phenomenon” following postictal depression. The very limited number of patients in the literature and also in our study does not allow us to determine the pathophysiology of PP. It seems that PP is a heterogeneous entity. Oshima et al.  suggested that PP should be subdivided into at least two types: a nuclear type representing the “classical picture of PP” as described by Kanner and Barry  and a second “atypical periictal type” that is caused by “epileptiform” discharge, mostly in limbic structures (temporal lobes, cingulate gyrus, etc.). Both our cases resemble the “atypical periictal type” as deﬁned by Oshima et al. . All previously cited reports [13–16], including our cases, show clearly that the EEG correlate of psychotic symptoms differs substantially from the ictal EEG correlate of epileptic seizures. In all of the mentioned cases, the EEG correlate of psychotic symptoms is
Table 1 Reported cases of psychotic symptoms during invasive EEG recording (in chronological order); Character and localization of invasive EEG ﬁnding (SSWC — sharp slow wave complexes; SWC spike slow wave complexes; L—left; R—right; SOZ — seizure onset zone). Reference
No. of patients
Localization of SOZ
Invasive EEG ﬁnding during psychotic symptoms (character)
Invasive EEG ﬁnding during psychotic symptoms (localization)
So et al.  Mathern et al.  Kanemoto  Seeck et al. 
1 1 1 1
L-mesiotemporal ??? L-mesiotemporal Bitemporal, bifrontal
Frequent interictal epileptiform discharges None SWC — rhythmic SSWC — semirhythmic
Takeda et al.  Schulze-Bonhage and van Elst 
L-mesiotemporal Both R-mesiotemporal
SWC — rhythmic None
Mesiotemporal, bilateral None L-amygdala, hippocampus L- anterior neocortical region (accompanied by increase of known lateral temporal spikes); no change frontally L-amygdala None
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rhythmic (or semi-rhythmic) and substantially slower than the ictal activity of each individual patient. Slow “rhythmicity” in these cases could be, in some cases, the “speciﬁc correlate” of the “atypical periictal type” of PP as deﬁned previously . Moreover, some PP could be associated with typical ictal discharge in limbic structures and in fact be the unrecognized cases of nonconvulsive epileptic status, i.e., ictal psychosis . Acknowledgments This work was supported by the project “CEITEC — Central European Institute of Technology” (CZ.1.05/1.1.00/02.0068) from European Regional Development Fund. Thanks to Anne Johnson for grammatical assistance. References  Schmitz B, Wolf P. Psychoses in epilepsy. In: Devinsky O, Theodore WH, editors. Epilepsy & behavior. New York: Liss-Wiley; 1991. p. 97–128.  Kanner AM, Stagno S, Kotagal P, Morris HH. Postictal psychiatric events during prolonged video-electroencephalographic monitoring studies. Arch Neurol 1996;53:258–63.  Kanemoto K, Kawasaki J, Kawai I. Postictal psychosis: a comparison with acute interictal and chronic psychoses. Epilepsia 1996;37:551–6.  Devinsky O. Postictal psychosis: common, dangerous, and treatable. Epilepsy Curr 2008;8:31–4.  Logsdail SJ, Toone BK. Post-ictal psychoses: a clinical and phenomenological description. Br J Psychiatry 1988;152:246–52.  Savard G, Andermann F, Olivier A, Rémillard GM. Postictal psychosis after partial complex seizures: a multiple case study. Epilepsia 1991;32:225–31.  Devinsky O, Abramson H, Alper K, et al. Postictal psychosis: a case control series of 20 patients and 150 controls. Epilepsy Res 1995;20:247–53.
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