Analogy between psychosis antedating epilepsy and epilepsy antedating psychosis

Purpose: Patients with recurrent epileptic seizures after the development of psychosis (Psychosis‐Epilepsy) have been regarded as belonging to a different clinical entity from those with epilepsy antedating the development of psychosis (Epilepsy‐Psychosis). However, clinical characteristics of patients with Psychosis‐Epilepsy have not been well described, except for early German studies. We aimed to estimate the reliability of distinction between Psychosis‐Epilepsy and Epilepsy‐Psychosis by comparing their clinical characteristics. Methods: Among 312 patients with epilepsy and psychosis enrolled in this multicenter study, 23 patients had Psychosis‐Epilepsy and 289 patients had Epilepsy‐Psychosis (i.e., interictal psychosis). Demographic (i.e., sex, age at time of evaluation, and intellectual functioning), psychiatric (i.e., age at onset of psychosis, subtype of psychosis, duration of psychotic episode, and a family history of psychosis), and epileptic (i.e., age at onset of epilepsy, subtype of epilepsy, seizure type, and a family history of epilepsy) characteristics of both groups were compared. Key Findings: Clinical characteristics, either in their psychoses or epilepsies, except for age‐related variables, were equivalent between patients with Psychosis‐Epilepsy and those with Epilepsy‐Psychosis. Time intervals between onset of psychosis and that of epilepsy in the two groups showed a normal distribution curve. Significance: The presence of many common features and the linear distribution of the time intervals did not fully support that Psychosis‐Epilepsy and Epilepsy‐Psychosis were two distinctly different entities. Among certain patients who have genetic vulnerabilities to both psychoses and seizures, psychosis may develop either antedating or postdating the development of epilepsy. These findings may suggest a necessary reconceptualization of psychoses in epilepsy.     

Difference in age of onset of psychosis between epilepsy and schizophrenia

To clarify the nature of psychosis development in epilepsy patients, we studied differences in age of onset of psychosis between epilepsy patients with psychosis (epilepsy-psychosis) and schizophrenia patients. Subjects were 282 patients with epilepsy-psychosis (36 postictal, 224 interictal, and 22 bimodal psychoses) and 612 schizophrenia patients. Age of onset was compared between the schizophrenia group and the whole epilepsy-psychosis group as well as its subgroups. Effects of sex and family history of psychosis on age of onset were also evaluated. Epilepsy patients developed psychosis later (mean age 30.1) than schizophrenia patients (mean age 26.6). Among epilepsy-psychosis subgroups, postictal psychosis and interictal psychosis showed a later onset than schizophrenia. In interictal psychosis, while chronic schizophrenia-like psychosis occurred at similar age compared to schizophrenia, brief episodic psychosis occurred at later age. Epilepsy-psychosis patients showed no sex difference in age of onset, whereas female schizophrenia patients showed a later onset than male schizophrenia patients. Both the epilepsy and schizophrenia patients with family history of psychosis tended to develop psychosis at an earlier age, although this did not reach statistically significant level. The findings of the study suggest that the nature of epilepsy-psychosis is not fully equivalent to that of schizophrenia.     

Frequency and age-related variables in interictal psychoses in localization-related epilepsies

PURPOSE: Several studies have described that patients with temporal lobe epilepsy (TLE) develop psychoses more frequently than patients with extra-temporal localization-related epilepsy (LRE). However, few controlled studies have demonstrated an increased susceptibility to psychosis in TLE patients. As one of a series of multi-center studies on psychosis in epilepsy, we investigated whether the frequency of interictal psychosis differs between types of LRE. METHODS: We reviewed some biological characteristics of 197 PE patients with interictal psychosis and of 456 LRE patients with no history of psychosis. Type of PE was determined as TLE, frontal lobe epilepsy, parietal lobe epilepsy, occipital lobe epilepsy, and multi-lobar epilepsy/undifferentiated lobar epilepsy by clinical symptoms, EEG findings, and neuroimaging. The frequency of psychosis for each type of LRE was compared. Ages at onset of epilepsy and psychosis and the time interval between onset of each were also analyzed. RESULTS: There was no significant correlation between psychosis and epilepsy type (P=0.211). Age-related variables also failed to show any significant differences between LRE types (age at onset of epilepsy, P=0.369; age at onset of psychosis, P=0.852; the time interval, P=0.893). CONCLUSIONS: Patients with LREs as well as with TLE are susceptible to interictal psychosis. The mean ages at onset of symptoms and the interval between onset of epilepsy and onset of psychosis that we observed suggest that patients with LREs, regardless of focus, may share similar processes in the development of psychiatric symptoms.     

Impact of antiepileptic drugs on genesis of psychosis

Opinions regarding the impact of antiepileptic drugs (AEDs) on the genesis of psychotic symptoms are varied. To re-examine this issue, the records of adult patients with partial epilepsy and newly added AEDs were retrospectively surveyed. The types of newly added AEDs and clinical characteristics were compared between 38 patients with active psychosis and 212 without psychotic history during a follow-up period of 3 to 6 months after initiation of AED administration. Using multivariate logistic regression analysis, the significance of possible predictive variables for development of psychosis was evaluated, which demonstrated that use of zonisamide (ZNS) and phenytoin (PHT), presence of complex partial seizures (CPS), and low intelligence level were significantly correlated with psychosis. We concluded that ZNS and PHT are possible risk factors for development of psychosis along with clinical variables, including the presence of CPS and low intelligence level.     

Five-year follow-up of patients with partial epilepsies in infancy

The aim of this study is to clarify the long-term outcome of patients with partial epilepsies that begin in the first 2 years of age. Thirty-nine infants who experienced partial epilepsies with onset by 2 years of age were followed until they were at least 5 years of age. Seizure and developmental outcome were investigated in relation to the following items: delayed psychomotor development before onset of seizures; interictal electroencephalogram (EEG) abnormalities; abnormal neuroimaging; family history of epilepsy; and history of neonatal seizures. Thirty-three infants achieved freedom from seizures and 27 achieved normal development. Delayed development before the onset and abnormal interictal EEG correlated with both poor seizure and developmental outcome. Abnormal neuroimaging findings correlated with a poor seizure outcome. A history of neonatal seizures and lack of a family history of epilepsy correlated with poor developmental outcome. The combination of the first four factors predicted a normal outcome with a sensitivity of 0.79 and a specificity of 0.87. The seizure and developmental outcomes were better in this study than those in previous studies. The combination of the four factors will be useful for predicting the outcomes in patients with partial epilepsies in infancy.     

The Absence of Interictal Spikes with Documented Seizures Suggests Extratemporal Epilepsy

PURPOSE: To determine the demographic and clinical characteristics of patients who have documented epileptic seizures on long-term video-EEG monitoring who do not have interictal spikes. METHODS: The records of 1,223 monitoring studies from 919 patients who underwent noninvasive long-term video-EEG monitoring were reviewed. In 28 patients (3.0% of monitored patients, 4.4% of patients with electrographic evidence of epilepsy), no interictal spikes were found despite the occurrence of at least one recorded electrographic seizure. The demographic, medical, neuropsychological, and EEG data of these patients were compared with those of 28 matched control patients with documented interictal spikes. RESULTS: Extratemporal seizures were significantly more frequent in the patients with at least one recorded epileptic seizure but without interictal spikes compared with patients with epileptic seizures and interictal spikes (p = 0.031). The only other significant difference between the groups (p = 0.016) was a later age at seizure onset (18.3 vs. 10.7 years) for the patients without interictal spikes. Age at evaluation, gender, handedness, clinical seizure type, family history of epilepsy, history of febrile seizures, neuropsychological testing, and neurologic and psychiatric history did not differ between the two groups. CONCLUSIONS: In patients with documented epilepsy without interictal spikes on EEG monitoring, the possibility of an extratemporal focus should be considered.     

Factors Affecting Epilepsy Development and Epilepsy Prognosis in Cerebral Palsy

A study was conducted between November 2006 and October 2009 to determine the factors predicting the presence and prognosis of epilepsy in patients with cerebral palsy. We enrolled 2 groups of patients: 42 with cerebral palsy in group 1 and 56 patients with cerebral palsy and epilepsy in group 2. The subjects in group 2 were considered to have good epilepsy prognosis if they were free of seizures for the previous year; otherwise they were considered to have poor epilepsy prognosis. In group 2, neonatal epilepsy, family history of epilepsy, and moderate to severe mental retardation were significantly higher than in group 1 (P < 0.05). In univariate analysis, neonatal seizures, epileptic activity as measured by electroencephalography, and polytherapy were found to be predictors of poor epilepsy prognosis. Additionally, the need for long-term medication to control seizures unfavorably affects prognosis. In logistic regression analysis, neonatal seizure and interictal epileptic activity in electroencephalography were found to be independent predictors of poor epilepsy outcome. In addition, logistic regression analysis revealed that increasing age reduces the success of epilepsy treatment. Neonatal seizures, family history of epilepsy, and mental retardation were found to be important and independent predictors of development of epilepsy in patients with cerebral palsy.     

Recurrent postictal psychosis after remission of interictal psychosis: further evidence of bimodal psychosis

PURPOSE: To ascertain whether bimodal psychosis (i.e., independent postictal and interictal psychosis) in patients with epilepsy can be characterized by postictal psychosis that develops after interictal psychosis remits. Methods: We reviewed the records of 14 patients with bimodal psychosis treated at a national center hospital.Clinical and psychopathological characteristics of the patients were examined. RESULTS: Among the 14 patients with bimodal psychosis, four initially had interictal psychosis, and 10 initially had postictal psychosis. That is, interictal-antecedent bimodal psychosis characterized four cases, and postictal-antecedent bimodal psychosis characterized 10 cases. Patients with interictal-antecedent bimodal psychosis composed 2.2% of the total patients with epilepsy and psychosis (n = 180) and 28.5% of total patients with bimodal psychosis. All four patients with interictal-antecedent bimodal psychosis had partial epilepsy with complex partial seizures, bilateral EEG abnormalities, and borderline (or decreased) intellectual functioning. Most of these clinical features are common to both types of bimodal psychosis. Among patients with interictal-antecedent bimodal psychosis, the mean age at the onset of the initial symptoms was 10.8 years (SD, 4.3 years) for epilepsy, 24.4 (6.1) years for interictal psychosis, and 33.8 (4.5) years for postictal psychosis. CONCLUSIONS: In a few patients, postictal psychosis develops after the remission of interictal psychosis. Interictal-antecedent bimodal psychosis is not likely a discrete entity because of several characteristics common to both types of bimodal psychosis. Patients may have greater vulnerability to psychosis and develop psychotic episodes easily, regardless of the presence of preceding seizures.     

Violence and Epilepsy: A Close Relation Between Violence and Postictal Psychosis

Summary: Purpose: We investigated the incidence of well-directed violent behavior and suicide attempts in patients with temporal lobe epilepsy, with special attention to postictal psychosis.
Methods: We compared 57 episodes of postictal psychosis with 62 episodes of acute interictal (or alternative) psychosis and with 134 complex partial seizures. All patients were matched for age and for age at onset of seizures.
Results: The incidence of well-directed violent behavior against human beings was significantly higher (23%) during postictal psychotic episodes than during acute interictal episodes (5%) and postictal confusion (1%). Suicide attempts were also more frequent during postictal psychosis (7%) than during either acute interictal psychosis (2%) or postictal confusion (0%).
Conclusions: Our study showed that well-directed violent and self-destructive behavior was not a feature of epileptic psychosis in general but a specific hallmark of postictal psychosis.     

Interictal psychotic episodes in epilepsy: duration and associated clinical factors

Purpose: There have been few reports showing the distribution of the duration of interictal psychosis (IIP) episodes and their association with clinical characteristics. To clarify the nature of IIP, we studied the duration of IIP episodes and their related factors. Methods: One hundred fifty‐five patients with epilepsy exhibited 320 IIP episodes during our follow‐up period (mean 16.9 years). The duration of all the episodes and the longest episode in each patient during the follow‐up periods were studied. Characteristics of the patients (e.g., epilepsy type, age of onset, and family history of psychosis) and episode‐specific factors (e.g., age of the episode, seizure frequency, administrations of antiepileptic drugs [AEDs] and antipsychotic drugs [APDs]) were analyzed in association with the duration of the episodes. Key Findings: Mean duration of the 320 IIP episodes was 82.7 weeks and that of the longest IIP episodes was 150.1 weeks. During the follow‐up period, 17 patients (11.0%) showed all episodes remitting within a month and 54 (34.8%) showed all episodes lasting for 6 months or longer. The IIP episodes that occurred at a younger age were often prolonged. Patients with a family history of psychosis or with early onset of psychosis tended to have more prolonged IIP episodes. Among the episodes treated with APDs, early administration of APDs was significantly associated with shorter IIP duration. Significance: The distribution of the duration of IIP episodes indicated the broad spectrum and heterogeneity of the IIP phenomena. The individual vulnerability to psychosis may be associated with prolonged episodes. Administration of APDs soon after onset of the episodes appeared to be effective in controlling them. These findings support empirical treatment principles for IIP to administer APDs at an early stage of its development.     

Reexamination of interictal psychoses based on DSM IV psychosis classification and international epilepsy classification

We sought to examine interictal psychoses based on the international epilepsy classification and DSM IV criteria, with special attention paid to epilepsy types as well as to subcategories of psychoses. One hundred thirty-two outpatients were studied, each with definite evidence of both epilepsy and interictal psychosis clearly demarcated from postictal psychosis. We compared them with 2,773 other epilepsy outpatients as a control. Risk factors for psychosis were examined within the temporal lobe epilepsy (TLE) group and the more extended group of symptomatic localization-related epilepsy. Further, nuclear schizophrenia and other nonschizophrenic psychotic disorders were compared. We confirmed a close correlation between TLE and interictal psychoses. Within the TLE group, only early epilepsy onset and a history of prolonged febrile convulsions were revealed to be significantly associated with interictal psychosis. Within the symptomatic localization-related epilepsy group, such parameters as complex partial seizures, autonomic aura, and temporal EEG foci were closely associated with psychoses. There was also a significant difference between groups as to ictal fear and secondary generalization. Whereas patients with early psychosis onset and a low intelligence quotient were overrepresented in the nuclear schizophrenia group, drug-induced psychosis and alternative psychosis were underrepresented. TLE proved to be preferentially associated with interictal psychoses. Within the TLE group, medial TLE in particular was found to be more closely associated with psychosis. Our data support the original postulation of Landolt, stating that alternative or drug-induced psychoses constitute a definite subgroup of interictal psychoses, which are different from chronic epileptic psychoses that simulate schizophrenia.     

A study of epilepsy-related psychosis

The association of epilepsy and psychosis is studied. Among the 500 patients of epilepsy evaluated, there were 12 patients, 8 males and 4 females with epilepsy-related psychosis. Their average age was 38 years. The interval between the age of onset of epilepsy and psychotic features was 9 years. Complex partial seizures were present in 7 patients and primary generalized tonic-clonic seizure was present in 1 patient. Four patients had post-ictal psychosis, 7 had acute interictal psychosis and 1 patient had chronic psychosis. The inter-ictal and chronic psychoses were schizophreniform whereas the post-ictal psychoses were not. EEG showed a temporal focus in 7 patients with complex partial seizures and an extra-temporal focus was identified in 4 out of the other 5 patients. Imaging (CT scan/MRI) revealed abnormalities in 10 patients. This study attempts to define the characteristics of psychoses occurring in epileptics.     

Partial Epilepsies in Infancy: A Study of 40 Cases

Forty patients with partial epilepsy that began before they were aged 3 years were recorded at the Centre Saint-Paul between 1981 and 1986 with a follow-up ranging from 1 year 9 months to 20 years. We analyzed the following data: age at onset, clinical features of seizures at onset and during the follow-up period, ictal and interictal EEG features, etiologic circumstances, evolution of the epilepsy, and psychomotor development. The age of onset was mostly between 2 months and 2 years (more than two thirds of cases). Most had partial symptomatic epilepsy. In nine cases, epilepsy was preceded by febrile convulsions. Seizures at onset were of the following type (in order of decreasing occurrence): unilateral seizures, complex partial seizures, elementary partial seizures, and other seizures, often difficult to classify. A few patients with infantile spasms associated with focal or multifocal EEG abnormalities, differing from West's syndrome, were included in this study. We discuss the problem arising from the classification of infantile seizures and epilepsies.     

Duration of postictal psychotic episodes

PURPOSE: To clarify duration of postictal psychosis (PIP) episodes and identify factors that influence its duration. METHODS: Fifty-eight patients with epilepsy exhibited 151 PIP episodes during a mean follow-up period of 12.8 years. Distribution of the duration of these episodes was determined, and factors potentially affecting were analyzed. Factors analyzed included PIP-related variables (i.e., antecedent seizures and the lucid interval) and patient characteristics (i.e., type of epilepsy, lateralization of EEG abnormalities, and intellectual functioning). RESULTS: The mean duration of the 58 first PIP episodes was 10.5 days, and that of all 151 PIP episodes (including multiple episodes) was 9.2 days. Approximately 95% of the PIP episodes resolved within 1 month. Most PIP-related variables, except for antipsychotic drugs administered, were not associated with duration of the episodes. Several patient characteristics, i.e., history of interictal psychosis, family history of psychosis, and intellectual functioning, were associated with duration of the PIP episodes. CONCLUSIONS: This study showed that most PIP episodes last less than 1 month. PIP episodes appear to be prolonged when individuals have an underlying vulnerability to psychosis. Clinical phenomena that can trigger PIP may not determine the course of the PIP episode.     

Spike frequency is dependent on epilepsy duration and seizure frequency in temporal lobe epilepsy.

OBJECTIVES: We wanted to investigate factors that are associated with frequency of interictal epileptiform discharges by investigating 303 patients with temporal lobe epilepsy (TLE). METHODS: We included all patients who consecutively underwent the adult presurgical evaluation program at our center and who had intractable, medial TLE with complex partial seizures due to unilateral medial temporal lobe lesions. The interictal EEG samples were automatically recorded and stored on computer. The location and frequency of interictal epileptiform discharges were assessed by visual analysis of interictal EEG samples of 2-minute duration every hour. RESULTS: There were 303 patients (aged 16-63) who met the inclusion criteria. The median interictal epileptiform discharge frequency was 15 IED/h, the median seizure frequency was 4 seizures/month. According to univariate analyses, we found that age at monitoring, epilepsy duration, and higher seizure frequency were associated with higher interictal epileptiform discharge frequency. In the logistic regression analysis, we found that higher seizure frequency (p < 0.001) and longer epilepsy duration (p = 0.007) were independently associated with higher spike frequency, while the age at monitoring was not. CONCLUSIONS: Seizure frequency and epilepsy duration (years of patient's life with seizure activity) were independently associated with IED frequency, suggesting that IED are modulated by seizures.     

Clinical aspects of epileptic psychosis in Brazil

We investigated a series of patients with epileptic psychosis in Brazil and compared our findings with those of other authors. We evaluated 38 outpatients with epileptic psychosis with a semistructured clinical interview, Annett inventory for hand dominance, international classifications for seizures and syndromes, and DSM-IV for psychosis diagnoses. We studied course and outcome for epilepsy and psychosis. Gender distribution was approximately even. Epilepsy and psychiatric disorders among relatives and early CNS insults in personal histories were frequent findings. Mean age of epilepsy onset was 9.3 years. Epilepsy started before psychosis in all cases, and evolved to clinical refractoriness. There was a predominance of temporal lobe epilepsy. Mean age of psychosis onset was 27.4 years, after a mean duration of epilepsy of 18.1 years, with predominance of schizophrenic presentations with interictal onset, frequent psychiatric admissions, suicide attempts, and postpsychosis functional decline. Tumors or lesions of an embryologic nature were uncommon, but mesial temporal sclerosis was frequent.     

Coexistence of focal and idiopathic generalized epilepsy in the same patient population.

PURPOSE: To review the clinical, electrographic, radiological, and pathological findings of patients with coexistent idiopathic generalized and partial epilepsy syndromes. METHODS: We performed a medical record review and a phone interview with all patients hospitalized to the Cleveland Clinic epilepsy monitoring unit (EMU) between 1992 and 2002 who fulfilled clinical and EEG criteria of coexistent partial and generalized epilepsy syndromes. RESULTS: Seven patients were identified. Two (29%) were men with a mean age of 26 years. Four had a history of febrile seizures. Family history was positive in five. Mean duration of the generalized epilepsy syndrome was 11 years, and of the focal epilepsy 18 years. An equal number of patients developed focal versus generalized epilepsy first. Interictal EEG activity was predominantly generalized. Four had video-EEG documentation of both types of seizures. In the rest, only focal seizures were recorded but interictal activity strongly suggested a coexistent generalized epilepsy. MRI showed hippocampal atrophy in all, and hippocampal dysplasia in three. Five patients had PET imaging, all with hypometabolism in areas corresponding to the ictal onset on EEG. Four patients underwent epilepsy surgery with good surgical outcome and pathological confirmation of hippocampal sclerosis in all. CONCLUSION: We found a 0.2% incidence of coexistent focal and primary generalized epilepsy. Febrile seizures and a positive family history were common. Good seizure control was achieved after temporal lobectomy, even when interictal generalized activity predominated.     

Are there physical risk factors for psychogenic non-epileptic seizures in patients with epilepsy?

Patients with epilepsy may have additional psychogenic non-epileptic seizures (PNES). It has been suggested that PNES are more common if patients with epilepsy are female, develop epilepsy later in life and have right-sided brain lesions. We examine whether these or other physical factors affect the risk of PNES in patients with epilepsy in a controlled study. METHODS: Ninety consecutive patients with PNES and concurrent epilepsy (PNES+E group) and 90 consecutive patients with epilepsy alone (epilepsy group) were compared with regard to the variables sex, age at onset of epilepsy, epilepsy type (focal/generalised), location and lateralisation of epileptogenic zone, aetiology of epilepsy, interictal epileptiform potentials, magnetic resonance imaging (MRI) abnormalities, neuropsychological (NPS) deficits and intelligence quotient (IQ). RESULTS: Female sex (P<0.001), abnormal visual memory (P=0.012), global NPS impairment (P=0.029), and low IQ category (P=0.005) were associated with a higher risk of PNES. Other variables did not differ between the groups. CONCLUSIONS: In patients with epilepsy, female sex, poor visual memory or global neuropsychological underperformance and low IQ are associated with an increased risk of PNES. MRI changes, epileptiform EEG abnormalities and location of epileptogenic zone do not show a predilection for one hemisphere.