Patient and control groups have similar features with respect to age and sex and there was a female dominance in both groups. Demographics, epilepsy history, seizure semiology, interictal, and ictal EEG findings and surgery outcomes were compared between the patient and control groups (Table 2). There was no significant difference between these 2 groups with respect to age of seizure onset, sex, age of seizure onset, history of febrile seizure, presence of pathologic findings detected by neurological examination, presence, and types of aura. Comparing the focal seizures with loss of consciousness, no marked difference was detected between the 2 groups while secondary generalized convulsion occurred more frequently in psychotic patients; however, the difference was not statistically significant (P=0.063).
In the medical history, psychotic patients had a significantly higher level of status epilepticus (P=0.002) and perinatal cerebral injury (P=0.042) while history of drug-resistant epilepsy was detected at a lower level (P=0.015).
After excluding all patients with known neuronal autoantibodies from EP and control groups, remaining 10 EP patients had still significantly more status epilepticus in the history (P=0.019 with Fishers exact test) and their EEG background activity tended to be slower (P=0.058). Also the rate of seizures with unknown origin is still higher in EP patients (P=0.0002), whereas the control group had more patients with TLE.
In terms of seizure semiology, the EP group was detected to have more seizures of unknown origin(P<0.0001), whereas the control group had significantly more characteristics indicating TLE (P<0.001). Although oroalimentary automatisms were more commonly observed in the control group (P=0.001), there was no marked difference between the 2 groups with respect to manual and pedal automatisms. Contralateral dystonia (P=0.003) and postictal nose wiping (P=0.002) was significantly more commonly observed in the nonpsychotic patients.
Investigation of the EEG results revealed that slow background activity was significantly common in the psychotic patients (P=0.009). Moreover bilateral interictal frontotemporal epileptogenic foci were observed more commonly among psychotic patients; however the difference was not statistically significant (P=0.07). Comparison of the study groups in terms of frontal intermittent rhythmic delta activity and fast rhythmic activity, revealed no significant difference. There was also no significant difference in lateralization and localization of the ictal onset between the 2 groups.
In the group of EP, there were 11 patients (73.3%) with drug-resistant course, whereas remaining patients has well-controlled epilepsy by using antiepileptic drugs. The retrospective survey showed that 5 of 15 patients with EP (33.3%) and 43 of 67 control patients (64.2%) had been operated (P=0.04). On the basis of the Engel classification, there was no significant difference between the 2 groups with respect to postoperative seizure control.
In terms of psychiatric symptoms, we observed that 4 of the 5 operated patients remained in good conditions for a period of at least 1 year after epilepsy surgery, but then these patients deteriorated even though their seizures were still controlled. The fifth patient without any change of psychosis had died during sleep with a possible sudden unexplained death in epilepsy.
Our results in a small group showed that slowing of the EEG background activity was more common in patients with EP in comparison to the control group. In addition, the group of psychotic patients had a significantly higher level of status epilepticus and perinatal cerebral injury in their past history. Thus, our findings may indicate a diffuse involvement of brain functioning that may relate to initial precipitating injuries, underlying both epilepsy and psychosis. Contrary to what we expected, EP patients were detected to exhibit less resistance to antiepileptic drugs compared with the control patients, mainly because of the high drug-resistance rate of the control group, randomly recruited from archive of the VEM unit. In this EP group, TLE was less common while seizures with unknown originwere more commonly observed.
In our study, we observed that psychosis was not correlated with age of seizure onset in EP patients. Except one study,15 previous studies performed in PP patients had also shown the absence of correlation between psychosis and age of seizure onset.2,16 There was no significant difference between the 2 groups; PP patients were detected to have similar findings with the literature.15,16 In PP and IIP patients, the history of status epilepticus was shown to be common.8 There are also studies reporting that status epilepticus and perinatal cerebral injury was not correlated to PP.15,16 In contrast, the absence of difference for the family history of epilepsy in the psychosis group may suggest that a marked genetic effect is not significantly involved in pathogenesis, as suggested by our results.
In contrast to previous studies, we detected no correlation between the presence of fear as aura (ictal fear) and EP.15,17 The lack of a correlation between PP and focal and generalized seizures was previously shown.15,16 Other studies reported a higher incidence of secondary generalized seizures among PP.2,8 In our study, secondarily generalized convulsion was more commonly observed in psychotic patients; however, the difference did not reach statistically significance level (P=0.063). This finding may be related to the fact that similar to status epilepticus and perinatal cerebral injury in the history, secondarily generalized convulsion may associate with more extensive cerebral involvement in related networks.
It is worth to emphasize that “ictal psychosis” is a highly controversial issue on many points including diagnostic spectrum, symptoms, and their time limits. Our 3 patients diagnosed with ictal psychosis have psychotic features starting at the same time with ictal EEG activity in VEM recording lasting about 0.5 to 1.5 minutes with an abrupt start and end. The patients described stereotypical hallucinations after the seizures when asked for it after regaining consciousness. In contrast, prolonged ictal psychotic states are rare and may occur as a nonconvulsive status epilepticus.6 DSM-4 criteria do not give a “time limit” for “psychotic disorder secondary to medical disease” which includes EP. Therefore we think that our patients could be considered as ictal psychosis, given that they satisfy these criteria. Interestingly, however, 2 of these patients developed IIP during the follow-up (one of them after a successful epilepsy surgery).
It was intriguing to note that, the EP group had a significantly high level of seizures of unknown origin while the control group had a significantly frequent level of TLE. This higher incidence of drug-resistant seizures originating from the temporal lobe, in our control group, may be attributed to the fact that patients with mesial temporal sclerosis represent the majority among patients, who were admitted to VEM unit for preoperative evaluation. Similarly, due to the same reason, oroalimentary automatisms, contralateral dystonia, and postictal nose wiping was significantly more common in the control group. The reason for this possible bias is that we randomly recruited the control group from the archives of the VEM unit, but selected all patients with EP who had undergone VEM investigation and in 4 of them this investigation was carried out only for differential diagnosis. These findings may also indicate that the patients with EP are more heterogenous than previously recognized with respect to ictal semiology. The high incidence of slowed background activity as well as of clinical initial precipitant factors such as status epilepticus ad perinatal cerebral injury also supported that psychosis may result from more extensive functional network disorder involving both hemispheres in these cases in contrast to a localized/lateralized involvement in temporal lobes.
It was also previously shown that psychosis and status epilepticus are related to autoimmune epilepsy and bilateral hippocampal sclerosis.18,19 As the encephalitic processes either overt or silent, related with these various known or unknown autoantibodies, often associated with cognitive and psychiatric symptoms in addition to seizures, it was reasonable to think that autoimmunity could be responsible for the etiology of EP in some patients. In contrast, the comparative analyses showed similar results after excluding the patients with detected autoantibodies.
From the view of the presence of psychosis that used to be considered as an obstacle for epilepsy surgery, only one third of patients with EP had been operated (Table 1). Although there was no significant difference between the 2 groups in postoperative seizure control as per Engel classification, these good postoperative results obtained in our small group of 5 psychotic patients are remarkable. We observed, however, that epilepsy surgery did not show any long-lasting benefits for psychotic symptoms in our small group of 4 patients. It is worth to emphasize that one of the operated patients with EP had deceased during sleep with a possible sudden unexplained death in epilepsy. Our experience in this small group may show that psychosis is not an absolute contraindication for surgery in EP patients with drug-resistant seizures.
The number of relevant studies is small and they usually involve the video-EEG findings of PP and IIP patients with TLE only.2,3 We, for the first time, investigated the clinical and video-EEG features of an unselected group with available long-term video-EEG studies including all psychosis subtypes for EP patients with frontal, temporal, and other seizures. Still, our study has certain limitations. As the study has a retrospective design, not all the EP patients could undergo VEM assessment, thus the sample size is limited. In addition, although EP patients were categorized into subtypes, no comparison could be made between these subgroups due to the small number of patients in each group and potential different clinical or electrophysiological characteristics could not be investigated.
In conclusion, our analysis of a small number of patients with heterogenous characteristics showed that patients with epilepsy and psychosis had more extensive interictal impairment of cerebral activity as reflected by the slowing of the EEG background and had certain initial precipitating factors. The good news is that some of them were responding well to antiepileptic drugs and a minority could also benefit from epilepsy surgery if a focus could be demonstrated.
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Keywords:Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
epilepsy; psychosis; video-EEG findings; mesial temporal sclerosis