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Summary: Purpose: Postictal psychosis is a well-known complication, occurring especially in patients with temporal lobe epilepsy. It usually runs a benign course. The literature on this topic is sparse, and the underlying pathogenic mechanisms are not known.
Methods: We report five patients with temporal lobe epilepsy in whom postictal psychosis developed during the course of video-EEG monitoring; they were studied with hexamethyl-propyleneamine-oxime single-photon emission computed tomography (HMPAO-SPECT) during and after the psychotic event.
Results: In comparison to the interictal state, all SPECT scans obtained during postictal psychosis were remarkable for bifrontal and bitemporal hyperperfusion patterns. Some studies also demonstrated unilateral left lateral frontal hyperperfusion. These cortical blood-flow patterns appeared to be distinct from those obtained during complex partial seizures.
Conclusions: Our data suggest that postictal psychoses in patients with temporal lobe epilepsy are associated with hyperactivation of both temporal and frontal lobe structures. This hyperperfusion may reflect ongoing (subcortical) discharges, active inhibitory mechanisms that terminate the seizure, or simply a dysregulation of cerebral blood flow.
The relation of psychosis and epilepsy has been an issue of interest since European psychiatrists in the early nineteenth century noted a high incidence of psychotic episodes in institutionalized patients with epilepsy (1,2). Although chronic interictal psychosis in patients with long-standing epilepsy has been studied in detail (3–6), postictal psychosis (PIP) has received relatively little attention (7–9). A clear temporal relation exists between the psychotic state and a precipitating series of tonic–clonic or even complex partial seizures, with a characteristic lucid interval lasting from several hours up to 6 days. The psychopathology of PIP is often polymorphic, with abnormal mood, paranoid delusions, and fluctuating impairment of consciousness and orientation being the symptoms most often reported (7). PIP accounts for ∼25% of psychoses in epilepsy (10) and was reported in 6.4% of all patients undergoing video-EEG monitoring at the Cleveland Clinic during a period of 18 months (11).
PIP usually runs a benign course, with remission of psychotic symptoms over several days, often without need for neuroleptic treatment (12). In rare cases, however, chronic psychoses may develop from recurrent or even a single episode of PIP (7,13). A possible relation between PIP and certain types of epilepsy has often been stressed but remains unclear. Whereas some authors reported a higher frequency of PIP in patients with focal epilepsies and complex partial seizures (7), others described a preponderance of generalized epilepsies (14).
PIPs have attracted some attention in the last decade because they are supposed to have a closer association with epileptogenesis than do interictal/chronic forms of epileptic psychoses. Nevertheless, the pathophysiology of PIP is not known.
Because single photon emission computed tomography (SPECT) offers the opportunity to visualize the three-dimensional dynamic changes of regional cortical blood flow (rCBF) associated not only with seizures but also with different types of psychiatric disorders, we think that it is especially suitable for the study of PIP, a condition in which epilepsy and psychosis are closely (temporally and maybe causally) related to each other.
We report five patients with temporal lobe epilepsy (TLE) in whom psychotic symptoms developed during video-EEG monitoring. In each patient, hexamethyl-propyleneamine-oxime (HMPAO)-SPECT scans were performed during PIP and after complete remission of psychotic symptoms to elucidate mechanisms possibly involved in the generation of PIP.
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We report five patients with TLE in whom PIP developed during or immediately after video-EEG monitoring. As compared with the symptom-free interval, individual SPECT scans apparently showed a global increase in CBF. After normalization of regional CBF to the global CBF, we compared individual ROIs and found a bitemporal and a mesial frontal and a unilateral left lateral frontal hyperperfusion pattern during PIP (see Fig. 4). The corresponding scalp EEG showed no significant change from the EEG of the interictal state and specifically no ictal EEG pattern. Therefore, our results suggest involvement of both temporal and frontal lobes in the generation of PIP.
Figure 4. Changes of regional cerebral blood flow (rCBF) during postictal psychosis (PIP). Shaded areas, brain regions hyperperfused on PIP scans as compared with interictal scans by regional indices >12% in each patient. Mean values for relative increase of rCBF in all patients: ITr, 22.4%; ITl, 20.9%; MTr, 17.6%; MTl, 17.9%; LFPl, 20.4%; MFr, 16.9%; MFl, 20.9%. BG, basal ganglia; BS, brainstem; C, central; CB, cerebellum; CD, caudate nucleus; IP, inferior parietal; IPA, inferior parietal anterior; IT, inferior temporal; ITA, inferior temporal anterior; ITP, inferior temporal posterior; LFA, lateral frontal anterior; LFP, lateral frontal posterior; LFS, lateral frontal superior; MF, mediofrontal; MT, mediotemporal; OA, occipital anterior; OF, orbitofrontal; OP, occipital posterior; PO, parietooccipital; SMA, supplementary motor area; SO, superior occipital; SP, superior parietal; STA, superior temporal anterior; STP, superior temporal posterior; TH, thalamus; TO, temporooccipital; VE, vermis; l, left; r, right.
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Studies on the mechanisms underlying PIP are few, and the results are inconsistent. An HMPAO-SPECT study performed by Fong et al. (18) in two patients with right TLE in whom PIP developed after video-EEG monitoring reported a marked right temporal and left basal ganglia hyperperfusion. The authors concluded that postictal cerebral hypofunction, similar to Todd paralysis, might not be the underlying mechanism of PIP, as was suggested by Savard et al. (8), who noted the clinical analogy of psychoses after complex partial seizures to other postictal phenomena such as postictal paresis. In contrast, the findings of focal hyperperfusion on ictal SPECT scans led Fong et al. (18) to the hypothesis that cerebral hyperactivation may lead to PIP. Similarly, Boylan (19), in her reply to the work of Fong et al., argued that the regional cerebral hyperperfusion during PIP was in good accordance with another SPECT study showing regional cerebral hyperperfusion in patients with postictal hemiparesis (20). A vascular “blush,” perhaps representing loss of cerebrovascular autoregulation at the side of the epileptogenic foci, might be the explanation for this hyperperfusion, as suggested by an angiogram performed during postictal hemiparesis (21). However, Boylan (22) presented the strongest argument against the hypofunction theory of Todd paralysis in PIP, which is the delayed onset of the phenomenon, as compared with the decrescendo course of Todd motor, cognitive, and visual phenomena.
The few depth-EEG studies performed during epileptic psychosis have yielded inconsistent results. One patient documented by So et al. (23) showed frequent bitemporal independent interictal epileptiform discharges, maximally involving mesial limbic structures, accompanied by slow-wave abnormalities, but no electrographic seizure activity. In contrast, a case report by Takeda et al. (24) described an increase in the frequency and duration of seizure discharges in the left amygdala when psychotic symptoms deteriorated, and a gradual decrease of seizure discharges, with psychotic symptoms remitting. However, the clinical course of this patient does not discount the possibility that the patient indeed had an ictal psychosis. Difficulties in differentiating PIP from complex partial status epilepticus can sometimes occur, as it has been documented impressively by Wieser (25), whose patient experienced prolonged anxiety, auditory hallucinations of songs, and dreamy recall during right temporal lobe status epilepticus. Similarly, Stevens and Lonsbury-Martin (26) suggested that subclinical limbic seizures could mediate apparently interictal psychopathology. Our own results could not definitely rule out the possibility that PIP was due to ongoing discharges, because no depth EEG recordings were performed. However, PIP in our patients differed from the preceding seizures in several aspects: (a) surface EEG showed no ictal discharges, although there was a slight increase in spike frequency; (b) the clinical seizure semiology was rather stereotyped in all complex partial seizures of each patient, differing markedly from symptoms during PIP; and (c) in two patients additionally, an ictal SPECT was available, showing circumscribed temporal hyperperfusion patterns in contrast to the scans obtained during psychosis.
Landolt (27,28) first described the phenomenon by which, in patients whose seizures came under control and whose EEGs became normal, psychotic symptoms developed, and he later called the phenomenon forced normalization. Forced normalization thus was defined as an EEG phenomenon, whereas its clinical counterpart with patients becoming psychotic when their seizures came under control and their psychosis resolving with the reoccurrence of seizures was referred to as alternative psychoses by Tellenbach (29). This concept of an association between epilepsy and psychosis was in contrast to the earlier hypothesis that some kind of antagonism between epilepsy and psychosis exists, which originally had led von Meduna (30) to introduce convulsive therapy for the treatment of schizophrenia. This apparent discrepancy was at least in part resolved by the concept of Wolf (31), who proposed that ongoing subcortical epileptic activity with an inhibitory surround is related to the phenomenon of PIP. Fong (18), in his reply to Boylan, suggested that ongoing abnormal electrical activities propagating via subcortical networks might cause PIP. Increased CBF, as found in our study in this context, may reflect such subcortical electrical activity as well as some inhibitory mechanisms terminating the cortical epileptic discharges either via increased active inhibition or via dysregulation of CBF. Postictal SPECT scans in patients without clinical relevant findings after seizure offset would add some valuable information to this hypothesis. However, such studies have not been performed because of ethical concerns.
Left lateralization of temporal lobe dysfunction was mentioned as a risk factor for epileptic psychosis, originally by Flor-Henry (32) in the late 1960s. Studies supporting the laterality hypothesis were later conducted by using SPECT (33–35), PET (36), and surface (37) and depth (5) EEG recordings, as well as neuropathologic (38) and neuropsychological (39) examinations. For PIP, our results suggest an involvement of both hemispheres in the development of PIP, because all patients had bilateral hyperperfusion patterns, although left lateralization in the lateral frontal region also was apparent in four of our five patients, regardless of the hemisphere of seizure onset. In addition, four of five patients showed bitemporal independent interictal epileptiform discharges, which points to involvement of both hemispheres. Although our patient group is too small to allow any generalizations, our results are supported by other studies that found an incidence of bilateral interictal epileptiform discharges in patients with PIP of ≤77%(8,23). Similarly, the interictal EEG in two patients with right-sided mesial TLE studied by Fong et al. (18) again showed bilateral abnormalities.
To conclude, our HMPAO-SPECT findings in five patients obtained during PIP suggest a hyperactivation of temporal and frontal lobe structures as one mechanism involved in the generation of PIP. Our findings enhance previous work on this area, supporting the hypothesis that PIP might be related to an increase in CBF. Elevated CBF in turn might be associated with inhibitory activity either through increased active inhibition or through dysregulation of cerebral blood flow. Alternatively, increased CBF might be associated with some ongoing electrical activity propagating via subcortical networks after termination of the seizure and suppression of its corresponding cortical discharges.