Bilateral volume reduction in posterior hippocampus in psychosis of epilepsy.

OBJECTIVE: Psychosis of epilepsy (POE) occurs more frequently in temporal lobe epilepsy, raising the question as to whether abnormalities of the hippocampus are aetiologically important. Despite decades of investigation, it is unclear whether hippocampal volume is reduced in POE, perhaps due to small sample sizes and methodological limitations of past research. METHODS: In this study, we examined the volume of the total hippocampus, and the hippocampal head, body and tail, in a large cohort of patients with POE and patients with epilepsy without psychosis (EC). One hundred adults participated: 50 with POE and 50 EC. Total and subregional hippocampal volumes were manually traced and compared between (1) POE and EC; (2) POE with temporal lobe epilepsy, extratemporal lobe epilepsy and generalised epilepsy; and (3) patients with POE with postictal psychosis (PIP) and interictal psychosis (IP). RESULTS: Compared with EC the POE group had smaller total left hippocampus volume (13.5% decrease, p<0.001), and smaller left hippocampal body (13.3% decrease, p=0.002), and left (41.5% decrease, p<0.001) and right (36.4% decrease, p<0.001) hippocampal tail volumes. Hippocampal head volumes did not differ between groups. CONCLUSION: Posterior hippocampal volumes are bilaterally reduced in POE. Volume loss was observed on a posteroanterior gradient, with severe decreases in the tail and moderate volume decreases in the body, with no difference in the hippocampal head. Posterior hippocampal atrophy is evident to a similar degree in PIP and IP. Our findings converge with those reported for the paradigmatic psychotic disorder, schizophrenia, and suggest that posterior hippocampal atrophy may serve as a biomarker of the risk for psychosis, including in patients with epilepsy.

Psychotic disorders induced by antiepileptic drugs in people with epilepsy.

Antiepileptic drug treatment can induce psychosis in some patients. However, there are no agreed definitions or diagnostic criteria for antiepileptic drug-induced psychotic disorder in the classification systems of either epileptology or psychiatry. In this study we investigated the clinical spectrum of antiepileptic drug-induced psychotic disorder in patients with epilepsy. The medical records of all patients with epilepsy who were diagnosed by a neuropsychiatrist as having a psychotic disorder at the Royal Melbourne Hospital from January 1993 to June 2015 were reviewed. Data were extracted regarding epilepsy and its treatment, psychotic symptoms profile and outcome. The diagnosis of epilepsy was established in accordance to the classification system of the International League Against Epilepsy while that of psychotic disorder was made according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition and the proposal on neuropsychiatric disorders in epilepsy. Patients with antiepileptic drug-induced psychotic disorder were compared to those with psychotic disorders unrelated to antiepileptic drugs assessed over the same period (non-antiepileptic drug induced psychotic disorder group). Univariate comparisons were performed and variables with a value of P < 0.1 were selected for the multivariate logistic regression analysis. The records of 2630 in-patients and outpatients with epilepsy were screened, from which 98 (3.7%) with psychotic disorders were identified. Among these, 14 (14.3%) were diagnosed to have antiepileptic drug-induced psychotic disorder. Excluding one patient who developed psychosis after valproate withdrawal, 76.9% in the antiepileptic drug induced psychotic disorder group were female and the percentage of temporal lobe involvement was higher in the antiepileptic drug induced psychotic disorder group (69.2% versus 38.1%, P < 0.05). Current use of levetiracetam was higher in antiepileptic drug-induced psychotic disorder group (84.6% versus 20.2%, P < 0.01) while use of carbamazepine was higher in the comparator group (15.4% versus 44.0%, P < 0.05). Multivariate logistic regression confirmed four factors associated with antiepileptic drug-induced psychotic disorder: female gender, temporal lobe involvement and use of levetiracetam, and a negative association with carbamazepine. Disorganized behaviours and thinking were more common in the antiepileptic drug-induced psychotic disorder group (100% versus 72.6% and 76.9% versus 38.1%, respectively; P < 0.05). The percentage of continuous treatment with antipsychotic drugs was lower in the antiepileptic drug-induced psychotic disorder group (15.4% versus 66.7%, P < 0.01). No patients experienced a chronic course in antiepileptic drug-induced psychotic disorder group whereas 40.5% did in non-antiepileptic drug induced psychotic disorder (P < 0.05). Our findings indicated that one in seven patients with epilepsy who developed psychosis had antiepileptic drug-induced psychotic disorder. In these patients, female gender, temporal lobe involvement and current use of levetiracetam were significantly associated with antiepileptic drug induced psychotic disorder compared to other types of psychosis, while carbamazepine had a negative association. Disorganized behaviours and thinking were predominant in antiepileptic drug-induced psychotic disorder. Patients with antiepileptic drug-induced psychotic disorder differed from non-antiepileptic drug-induced psychotic disorders in having better outcome.

Neuropsychological function in psychosis of epilepsy.

OBJECTIVE: The neuropsychological profile of patients with psychosis of epilepsy (POE) has received limited research attention. Recent neuroimaging work in POE has identified structural network pathology in the default mode network and the cognitive control network. This study examined the neuropsychological profile of POE focusing on cognitive domains subserved by these networks. METHODS: Twelve consecutive patients with a diagnosis of POE were prospectively recruited from the Comprehensive Epilepsy Programmes at The Royal Melbourne, Austin and St Vincent's Hospitals, Melbourne, Australia between January 2015 and February 2017. They were compared to 12 matched patients with epilepsy but no psychosis and 42 healthy controls on standardised neuropsychological tests of memory and executive functioning in a case-control design. RESULTS: Mean scores across all cognitive tasks showed a graded pattern of impairment, with the POE group showing the poorest performance, followed by the epilepsy without psychosis and the healthy control groups. This was associated with significant group-level differences on measures of working memory (p = < 0.01); immediate (p = < 0.01) and delayed verbal recall (p = < 0.01); visual memory (p < 0.001); and verbal fluency (p = 0.02). In particular, patients with POE performed significantly worse than the healthy control group on measures of both cognitive control (p = .005) and memory (p < .001), whereas the epilepsy without psychosis group showed only memory difficulties (delayed verbal recall) compared to healthy controls (p = .001). CONCLUSION: People with POE show reduced performance in neuropsychological functions supported by the default mode and cognitive control networks, when compared to both healthy participants and people with epilepsy without psychosis.

Psychiatric history does not predict seizure outcome following temporal lobectomy for mesial temporal sclerosis.

PURPOSE: A lifetime psychiatric history has been reported to be associated with poorer seizure outcome following temporal lobectomy for drug-resistant focal epilepsy, but it remains unclear whether this is confounded by the nature of the epileptogenic pathology. Here we examined this association in a pathologically homogeneous group of patients with mesial temporal sclerosis (MTS). METHODS: The study population included 72 consecutive patients who underwent a temporal lobectomy for drug resistant temporal lobe epilepsy (TLE) and had histopathologically proven MTS. All patients were assessed preoperatively by a neuropsychiatrist. Chi-square analysis was undertaken to look for demographic, clinical, psychiatric, or neurologic factors associated with seizure outcome at 1 year. The relationship between having a psychiatric disorder and seizure outcome was examined by generating Kaplan-Meier curves and comparing between groups the log rank test as well as generating Cox regression models to estimate hazard ratios. KEY FINDINGS: There were no significant associations between postsurgery seizure outcome and a current or lifetime history of any psychiatric disorder. SIGNIFICANCE: A history of psychiatric disorder, in particular depression and psychosis, is not associated with a poorer surgical outcome in patients with MTS. These findings have implications for the clinical management of patients under consideration for temporal lobectomy.

Increased cortical thickness in nodes of the cognitive control and default mode networks in psychosis of epilepsy.

OBJECTIVE: To explore the cortical morphological associations of the psychoses of epilepsy. METHODS: Psychosis of epilepsy (POE) has two main subtypes - postictal psychosis and interictal psychosis. We used automated surface-based analysis of magnetic resonance images to compare cortical thickness, area, and volume across the whole brain between: (i) all patients with POE (n = 23) relative to epilepsy-without psychosis controls (EC; n = 23), (ii) patients with interictal psychosis (n = 10) or postictal psychosis (n = 13) relative to EC, and (iii) patients with postictal psychosis (n = 13) relative to patients with interictal psychosis (n = 10). RESULTS: POE is characterised by cortical thickening relative to EC, occurring primarily in nodes of the cognitive control network; (rostral anterior cingulate, caudal anterior cingulate, middle frontal gyrus), and the default mode network (posterior cingulate, medial paracentral gyrus, and precuneus). Patients with interictal psychosis displayed cortical thickening in the left hemisphere in occipital and temporal regions relative to EC (lateral occipital cortex, lingual, fusiform, and inferior temporal gyri), which was evident to a lesser extent in postictal psychosis patients. There were no significant differences in cortical thickness, area, or volume between the postictal psychosis and EC groups, or between the postictal psychosis and interictal psychosis groups. However, prior to correction for multiple comparisons, both the interictal psychosis and postictal psychosis groups displayed cortical thickening relative to EC in highly similar regions to those identified in the POE group overall. SIGNIFICANCE: The results show cortical thickening in POE overall, primarily in nodes of the cognitive control and default mode networks, compared to patients with epilepsy without psychosis. Additional thickening in temporal and occipital neocortex implicated in the dorsal and ventral visual pathways may differentiate interictal psychosis from postictal psychosis. A novel mechanism for cortical thickening in POE is proposed whereby normal synaptic pruning processes are interrupted by seizure onset.

Clinical characteristics and outcome in patients with psychogenic nonepileptic seizures.

OBJECTIVES: To examine baseline clinical features of psychogenic nonepileptic seizures (PNES) in a large cohort and to investigate outcome over a period of up to 10 years. Studies investigating PNES have been limited by differences in diagnostic criteria, short follow-up periods, and the use of limited outcome measures. METHOD: Patients with PNES were identified, using strict diagnostic criteria. Baseline neurological, neuropsychiatric, and neuroimaging data were obtained from medical records. Long-term outcome was assessed with ratings of seizures, psychopathology, and quality of life in a subset of the patients. RESULTS: Patients with PNES (n = 221) experienced long delays in diagnosis (mu, 5.6 years; standard deviation, 7.7 years) and high rates (>60%) of prolonged treatment with antiepileptic drugs. Compared with previous studies, a relatively low proportion (8.1% to 17.9%, depending on diagnostic criteria) had comorbid epilepsy. An unexpected finding was that 22.6% of PNES patients had magnetic resonance imaging abnormalities. Patients assessed at follow-up (n = 61) exhibited poor long-term outcomes with ongoing PNES, high rates of psychopathology, low rates of specialist follow-up, poor quality of life, and poor overall levels of functioning. CONCLUSIONS: These results demonstrate the need for earlier diagnosis of PNES and comorbidities and highlight the need for diagnostic and therapeutic approaches that combine neurological and psychiatric perspectives.

Liaison psychiatry in a central nervous system tumor service.

BACKGROUND: Tumors of the central nervous system (CNS) have physical and psychological effects that commonly interact and change over time. Although well suited to addressing problems at the interface between physical and psychological medicine, the role of the consultation-liaison psychiatrist has not been previously described in the management of these patients. The purpose of this paper is to summarize the experience of psychiatry liaison attachment within a CNS tumor service and to reflect on its utility within a complex multidisciplinary environment. METHODS: A retrospective file review was performed on all cases seen by a psychiatrist in a CNS tumor service over the previous 5 years. A simple thematic inductive analysis was conducted of the common problems experienced by patients and their management by the psychiatrist and within the team. RESULTS: Five common themes were identified: (i) facilitating adaptation to diagnosis; (ii) supporting living with lower-grade tumors; (iii) managing mental disorders; (iv) neuropsychiatric symptoms of tumor progression; and (v) grief and uncertainty in the advanced stages of illness. The capacity of the psychiatrist to understand and integrate the clinical, pathological, radiological, and treatment information, in communication with colleagues, helped address these challenges. CONCLUSIONS: Psychological challenges in CNS tumor patients have both psychological and neurological underpinnings. In our experience, the addition of a liaison psychiatrist to a CNS tumor service was efficient and effective in improving patient management and led to enhanced communication and decision-making within the team.

Psychosis with obsessive-compulsive symptoms in tuberous sclerosis.

We present a case of tuberous sclerosis complex (TSC) diagnosed in adulthood in a man initially referred for specialist neuropsychiatric assessment with psychosis and obsessive-compulsive symptoms (OCS) on a background of epilepsy and intellectual disability. To our knowledge, this is the first reported patient with TSC featuring both psychosis and OCS. This patient highlights the importance of comprehensive re-evaluation of atypical presentations of intellectual disability, epilepsy and associated neuropsychiatric symptoms, even in adulthood. This is particularly relevant in the context of significant advances in genetics, neuroscience, imaging and treatments for heritable neurogenetic disorders.

Neuropsychiatric morbidity in focal epilepsy.

BACKGROUND: Previous work has identified elevated prevalence rates for psychiatric disorders in individuals with medically refractory focal epilepsy, particularly temporal lobe epilepsy. Many studies were undertaken before the advent of video electroencephalogram monitoring (VEM) and magnetic resonance imaging (MRI). AIMS: To investigate which characteristics of the focal epilepsy syndromes are associated with the presence of depression or psychosis. METHOD: Three hundred and nineteen individuals with focal epilepsy admitted for VEM were seen over an 11-year period. The lifetime history of depression and psychosis, epileptic site, laterality and type of lesion were determined by clinical assessment, VEM and MRI scan. RESULTS: There was a significant association between the prevalence of depressive symptoms and non-lesional focal epilepsy. There were no significant differences in prevalence of neuropsychiatric disorders between the groups with temporal lobe epilepsy and those with extratemporal lobe epilepsy. CONCLUSIONS: These findings contrast with previous findings in smaller cohorts. The association between non-lesional focal epilepsy and depression may be due to the effects of a more diffuse epileptogenic area.