Dissociation in patients with dissociative seizures: relationships with trauma and seizure symptoms.

BACKGROUND: This study aimed to extend the current understanding of dissociative symptoms experienced by patients with dissociative (psychogenic, non-epileptic) seizures (DS), including psychological and somatoform types of symptomatology. An additional aim was to assess possible relationships between dissociation, traumatic experiences, post-traumatic symptoms and seizure manifestations in this group. METHOD: A total of 40 patients with DS were compared with a healthy control group (n = 43), matched on relevant demographic characteristics. Participants completed several self-report questionnaires, including the Multiscale Dissociation Inventory (MDI), Somatoform Dissociation Questionnaire-20, Traumatic Experiences Checklist and the Post-Traumatic Diagnostic Scale. Measures of seizure symptoms and current emotional distress (Hospital Anxiety and Depression Scale) were also administered. RESULTS: The clinical group reported significantly more psychological and somatoform dissociative symptoms, trauma, perceived impact of trauma, and post-traumatic symptoms than controls. Some dissociative symptoms (i.e. MDI disengagement, MDI depersonalization, MDI derealization, MDI memory disturbance, and somatoform dissociation scores) were elevated even after controlling for emotional distress; MDI depersonalization scores correlated positively with trauma scores while seizure symptoms correlated with MDI depersonalization, derealization and identity dissociation scores. Exploratory analyses indicated that somatoform dissociation specifically mediated the relationship between reported sexual abuse and DS diagnosis, along with depressive symptoms. CONCLUSIONS: A range of psychological and somatoform dissociative symptoms, traumatic experiences and post-traumatic symptoms are elevated in patients with DS relative to healthy controls, and seem related to seizure manifestations. Further studies are needed to explore peri-ictal dissociative experiences in more detail.

Epilepsy-related psychosis: a role for autoimmunity?

Postictal psychosis (PIP) is a serious psychiatric complication of epilepsy that occurs in approximately 6% of patients following multiple complex partial or generalized seizures. The psychosis is classically described as having a pleomorphic phenomenology, including paranoid, grandiose, and religious delusions as well as multimodal hallucinations with prominent affective changes and agitation. Little is understood about the pathophysiology of the condition. There has been a recent increase in interest in the relevance of autoimmunity to the pathogenesis of both epilepsy and psychosis. Studies have demonstrated the presence of antibodies directed against synaptic autoantigens (such as the N-methyl-d-aspartate receptor or the voltage-gated potassium channel complex) in approximately 10% of cases of sporadic epilepsy. These same autoantibodies are known to cause encephalopathy syndromes which feature psychiatric symptoms, usually psychosis, as a prominent part of the phenotype as well as other neurological features such as seizures, movement disorders, and autonomic dysfunction. It is beginning to be asked if these antibodies can be associated with a purely psychiatric phenotype. Here, we hypothesize that PIP may be an autoimmune phenomenon mediated by autoantibodies against synaptic antigens. More specifically, we outline a potential mechanism whereby long or repeated seizures cause short-lived blood-brain barrier (BBB) dysfunction during which the brain becomes exposed to pathogenic autoantibodies. In essence, we propose that PIP is a time-limited, seizure-dependent, autoantibody-mediated encephalopathy syndrome. We highlight a number of features of PIP that may be explained by this mechanism, such as the lucid interval between seizures and onset of psychosis and the progression in some cases to a chronic, interictal psychosis.

Psychologic treatment of functional neurologic disorders.

The management of patients with functional neurologic disorders poses many challenges. Psychologic treatments may well start at the point of delivery of the diagnosis, when careful explanations about the nature of the disorder have to be given to the patient and possibly also relatives/carers. Different conceptual models may assist in explaining the factors underlying the presentation, two of which (functional and dissociative) are briefly outlined here. The challenges for neurologists and psychiatrists of delivering a psychologic formulation as part of the diagnosis delivery are considered, along with the importance of clear communication between professionals involved in the patient's care. Existing literature on treatments incorporating psychologic components suggests that, despite limitations in the study designs and the potential bias in some outcome evaluations, there is evidence to support the use of psychologic interventions for at least some functional neurologic disorders, although larger and better-designed studies are required in this area.

The approach to patients with "non-epileptic seizures".

Up to one fifth of patients who present to specialist clinics with seizures do not have epilepsy. The majority of such patients suffer from psychologically mediated episodes; dissociative seizures, often referred to as "non-epileptic seizures". This paper describes the diagnostic evaluation of seizure disorders, including clinical assessment and the role of special investigations. The organic and psychiatric imitators of epilepsy are outlined and findings on psychiatric assessment are reviewed. This group of patients often proves difficult to engage in appropriate treatment and an approach to explaining the diagnosis is described. As yet there are no controlled trials of treatment in this disorder but preliminary evidence suggests cognitive behavioural therapy is both a rational and promising way forward.

Neural correlates of working memory in a visual letter monitoring task: an fMRI study.

Complex mental operations rely on the coordinated activity of widely distributed brain regions constituting neurocognitive networks. Using multislice echoplanar functional magnetic resonance imaging (fMRI) we have contrasted regional brain activity during a control and an experimental condition which differed with respect to the demands placed on verbal working memory. Subjects were seven right-handed healthy male volunteers. Analysis of group and individual data revealed activation in the anterior and posterior parasagittal cortex in all subjects, left parietal cortex (six subjects) and left dorsolateral prefontal cortex (five subjects). These results suggest that verbal working memory is subserved by a neurocognitive network comprising cortical regions involved in attention, executive function and short term mnemonic processes.

Auditory hallucinations inhibit exogenous activation of auditory association cortex.

Percepts unaccompanied by a veridical stimulus, such as hallucinations, provide an opportunity for mapping the neural correlates of conscious perception. Functional magnetic resonance imaging (fMRI) can reveal localized changes in blood oxygenation in response to actual as well as imagined sensory stimulation. The safe repeatability of fMRI enabled us to study a patient with schizophrenia while he was experiencing auditory hallucinations and when hallucination-free (with supporting data from a second case). Cortical activation was measured in response to periodic exogenous auditory and visual stimulations using time series regression analysis. Functional brain images were obtained in each hallucination condition both while the patient was on and off antipsychotic drugs. The response of the temporal cortex to exogenous auditory stimulation (speech) was markedly reduced when the patient was experiencing hallucinating voices addressing him, regardless of medication. Visual cortical activation (to flashing lights) remained normal over four scans. From the results of this study and previous work on visual hallucinations we conclude that hallucinations coincide with maximal activation of the sensory and association cortex, specific to the modality of the experience.

Activation of area V5 by visual perception of motion demonstrated with echoplanar MR imaging.

Cortical activation in visual association areas known to be responsible for the perception of motion was investigated in two volunteers who viewed a projected animated cartoon periodically "run" and "frozen" during collection of echoplanar MR images. Ten axial, contiguous, 5 mm thick, T2-weighted, gradient-echo images (TE 40 ms, TR 3000 ms) depicting BOLD contrast were acquired through the occipital lobe using a GE Signa 1.5 T system with an advanced NMR operating console. Images were analysed by time series regression modelling estimating power in the MR signal at the ON-OFF frequency of motion. Highly significant activation in response to motion perception was identified in both subjects bilaterally in area V5.

Functional echoplanar brain imaging correlates of amphetamine administration to normal subjects and subjects with the narcoleptic syndrome.

Two subjects with narcoleptic syndrome and three healthy volunteers underwent functional magnetic resonance imaging during the simultaneous presentation of periodic auditory and visual stimuli both before and after administration of amphetamine. The effect of amphetamine in control subjects was a small reduction in the extent of sensory-induced activation. In the narcoleptic subjects, amphetamine led to an increase in the extent of induced activation within primary and association sensory cortex.

Cognitive behaviour therapy with adults with intractable epilepsy and psychiatric co-morbidity: preliminary observations on changes in psychological state and seizure frequency.

Cognitive behaviour therapy (CBT) was undertaken with six adults with chronic, poorly controlled seizures and co-existing psychiatric and/or psychosocial difficulties. During 12 sessions of CBT from an experienced CBT Nurse Specialist, treatment focused concurrently on epilepsy-related problems, associated psychopathology and on the development of psychological strategies to reduce seizure occurrence. At the end of treatment participants rated their initial epilepsy-related problem as having less impact on their daily lives and at one-month follow-up reported less deleterious impact on everyday life in terms of their psychological difficulties. In addition participants demonstrated significant improvements in terms of their self-rated work and social adjustment, and in their decreased use of escape-avoidance coping strategies. These positive findings occurred despite the absence of a significant decrease in seizure frequency. Issues raised by the complexity and severity, both of these patients' psychological/psychosocial difficulties and their epilepsy, are discussed in relation to the optimal length of treatment that may be required when adopting a CBT model in this patient group.

Risk factors of female HIV-seropositive patients attending the clinic for sexually transmitted diseases at St Mary's Hospital, London.

Of 3450 women tested for antibodies to human immunodeficiency virus HIV-1 and HIV-2 between September 1985 and July 1989, 61 were positive (1.8%). Twenty-seven of these (44%) were presumed to have acquired their HIV infection by heterosexual contact and 23 (38%) were intravenous drug addicts. In geographical origin, 23 (38%) of the patients were from the UK and 19 (31%) from Africa. Amongst these 61 women, 2 (3%) have since died, one committed suicide and one was suspected of committing suicide.

Dissociation, hypnotizability, coping styles and health locus of control: characteristics of pseudoseizure patients.

Although literature in this area is relatively sparse, the occurrence of psychogenic non-epileptic seizures (pseudoseizures) has been linked to stress, anxiety and possible dissociative tendencies. An association between dissociation and hypnotic susceptibility has also been proposed and dissociative tendencies have themselves been found to relate to the use of emotion-focused coping strategies. In order to investigate the hypothesis that pseudoseizure patients may exhibit higher levels of dissociation, a more emotion-focused coping style, and greater hypnotic susceptibility than the general population, the questionnaire responses of 20 patients with pseudoseizures were compared with those obtained from a non-clinical control group. As predicted, pseudoseizure patients demonstrated some evidence of higher levels of dissociation and escape-avoidance coping strategies. They also expressed a greater belief in external control over health and higher depression scores, compared to the control group, but the previously reported elevation in hypnotizability scores in the pseudoseizure patients was not found. Possible explanations for this pattern of results are discussed.

Cognitive-behavioral therapy for psychogenic nonepileptic seizures: a pilot RCT.

OBJECTIVE: To compare cognitive-behavioral therapy (CBT) and standard medical care (SMC) as treatments for psychogenic nonepileptic seizures (PNES). METHODS: Our randomized controlled trial (RCT) compared CBT with SMC in an outpatient neuropsychiatric setting. Sixty-six PNES patients were randomized to either CBT (plus SMC) or SMC alone, scheduled to occur over 4 months. PNES diagnosis was established by video-EEG telemetry for most patients. Exclusion criteria included comorbid history of epilepsy, <2 PNES/month, and IQ <70. The primary outcome was seizure frequency at end of treatment and at 6-month follow-up. Secondary outcomes included 3 months of seizure freedom at 6-month follow-up, measures of psychosocial functioning, health service use, and employment. RESULTS: In an intention-to-treat analysis, seizure reduction following CBT was superior at treatment end (group x time interaction p < 0.0001; large to medium effect sizes). At follow-up, the CBT group tended to be more likely to have experienced 3 months of seizure freedom (odds ratio 3.125, p = 0.086). Both groups improved in some health service use measures and on the Work and Social Adjustment Scale. Mood and employment status showed no change. CONCLUSIONS: Our findings suggest that cognitive-behavioral therapy is more effective than standard medical care alone in reducing seizure frequency in PNES patients. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that CBT in addition to SMC, as compared to SMC alone, significantly reduces seizure frequency in patients with PNES (change in median monthly seizure frequency: baseline to 6 months follow-up, CBT group, 12 to 1.5; SMC alone group, 8 to 5).

Ictal symptoms of anxiety, avoidance behaviour, and dissociation in patients with dissociative seizures.

OBJECTIVE: To examine anxiety related seizure symptoms and avoidance behaviour in adults with dissociative (psychogenic non-epileptic) seizures (DS) in comparison with a group suffering from partial epilepsy. METHODS: 25 DS and 19 epilepsy patients completed an attack symptom measure, the hospital anxiety and depression scale, the dissociative experiences scale, and the fear questionnaire. RESULTS: DS patients reported the presence of significantly greater numbers of somatic symptoms of anxiety during their attacks than the epilepsy group, despite not reporting subjectively higher levels of anxiety. The DS patients also reported higher levels of agoraphobic-type avoidance behaviour than the epilepsy group. Measures of dissociation were higher in the DS group, who also reported greater symptoms of depression. CONCLUSIONS: The findings support a model whereby DS occur as a paroxysmal, dissociative response to heightened arousal in the absence of raised general anxiety levels. The model has practical implications for clinical assessment and treatment: in clinical practice, inquiry about these symptoms may help in the diagnosis of DS; with respect to treatment, the anxiety related symptoms and avoidance behaviour prevalent in DS are a potential focus for a cognitive behavioural approach analogous to that used in the treatment of other anxiety disorders.

Psychotic and depressive symptoms in Parkinson's disease. A study of the growth hormone response to apomorphine.

BACKGROUND: The growth hormone (GH) response to apomorphine, thought to reflect central dopaminergic receptor sensitivity, has been reported as enhanced in acute schizophrenia. We investigated this response in relation to the psychotic episodes associated with Parkinson's disease (PD). METHOD: The GH response to apomorphine was measured in three groups of patients with Parkinson's disease: those currently psychotic (n = 9), those with a past history of psychosis (n = 7) and those who had never been psychotic (n = 8). RESULTS: Apomorphine-induced GH response was not related to psychosis but was unexpectedly associated with measures of depression. CONCLUSIONS: Visual hallucinations were a prominent feature in the psychotic patients and the atypical nature of these psychoses might explain why we found no evidence of dopaminergic sensitivity. Serotonergic dysfunction would be in keeping with this. Dopaminergic mechanisms may contribute to the minor depressive symptomatology seen in PD.

A neuropsychological comparison of schizophrenia and schizophrenia-like psychosis of epilepsy.

BACKGROUND: The schizophrenia-like psychoses of epilepsy (SLPE) might represent a secondary form of schizophrenia in which the pathology is relatively confined to the temporal lobe. To test this possibility we have compared the neuropsychological profile of schizophrenia and SLPE. Our main hypothesis was that both psychotic groups would show deficits of temporal lobe function but that prefrontal impairment, as measured by tests of executive function, would be found only in the primary schi ophrenic group. METHODS: Four groups were studied: (1) patients with SLPE (N = 25); (2) patients with epilepsy but not psychiatric history (N = 24); (3) patients with schizophrenia (N = 22); and (4) healthy volunteers (N = 24). Neuropsychological testing comprised measures of pre-morbid IQ, current verbal and performance IQ, information processing, digit span, motor speed, verbal and visual learning and memory, verbal fluency, the Wisconsin Card Sorting Task, the Stroop test and the trail making task. RESULTS: Patients with schizophrenia and those with SLPE had almost identical neuropsychological profiles, with impairments of attention, episodic memory (verbal > visual) and executive function. The epileptic controls showed similar though less severe impairments of memory and of some tests of executive function. CONCLUSIONS: Our results do not support the hypothesis that the pathophysiology of SLPE and schizophrenia are distinct. While our findings suggest an important role for dominant temporal lobe abnormality in schizophrenia, both in its primary form and in that occurring in patients with epilepsy, they also implicate generalized cognitive impairment, manifest in particular as attentional deficits, in both forms of the disorder.

Schizophrenia, temporal lobe epilepsy and psychosis: an in vivo magnetic resonance spectroscopy and imaging study of the hippocampus/amygdala complex.

BACKGROUND: We have used proton magnetic resonance imaging and spectroscopy to measure hippocampus/amygdala volumes and anterior hippocampal metabolite concentrations (N-acetyl aspartate (NAA), creatine/phosphocreatine and choline) in subjects with temporal lobe epilepsy (TLE), schizophrenia and in normal controls. METHOD: Four groups of right-handed patients were selected: 12 with TLE and psychosis (EP), 12 with TLE and no psychosis (ENP), 26 with schizophrenia, and 38 normal controls. Imaging and spectroscopy were performed with a 1.5T Signa GE scanner. RESULTS: The schizophrenia group showed a significant left-sided reduction in all metabolites. In the epilepsy groups NAA was reduced bilaterally. The NAA reduction in the EP group was greater than in the ENP group, especially on the left, although the result did not reach significance. Total hippocampus/amygdala volumes showed no significant differences in any of the groups when compared with normal controls. When compared with controls significant, specific regional volume reductions were present bilaterally in the EP group and in the left hippocampus/amygdala in schizophrenia. The regional volume reduction found in schizophrenia was also present in EP but not in ENP. CONCLUSION: Spectroscopic abnormalities were more pronounced in the epilepsy groups and were bilateral, and abnormalities in schizophrenia were left sided. Specific regional hippocampus/amygdala volume reductions were more marked in the EP group and were bilateral. Left-sided regional volume reduction identified in the dominant hemisphere of schizophrenics was also present in EP patients, but not in ENP, suggesting that this region in the left temporal lobe may be significant in the aetiology of psychosis. This is further supported by the predominantly left-sided NAA reduction in schizophrenia. High resolution morphometric studies may identify specific regions of the brain associated with the development of psychosis.

Inter-rater and temporal reliability of the Standardized Assessment of Personality and the influence of informant characteristics.

The Standardized Assessment of Personality (SAP) is a short, semi-structured interview designed to be used with an informant of the patient. The informants of 52 patients were interviewed separately by two raters for an inter-rater reliability study. The overall level of agreement was excellent, kappa = 0.76, with a range between 0.60 and 0.82 for the individual categories of personality disorder. For a temporal reliability study, the relatives of 77 patients were interviewed. The overall level of agreement was good, kappa = 0.65, with a range between 0.54 and 0.79 for individual categories. Characteristics of informants whose reports were rated with greater levels of reliability were female gender and greater length of acquaintance with the patient.

Pseudoseizures and asthma.

BACKGROUND: Sexual abuse and head injury are important risk factors of pseudoseizures, reported in about a third of patients. Clinical experience suggests that asthma is another possible risk factor. OBJECTIVES: To determine the relative prevalence of asthma in patients with pseudoseizures. METHODS: A retrospective record review was undertaken of reported asthma in 102 patients with pseudoseizures and 70 psychotic controls. The pseudoseizure patients were subgrouped according to method of diagnosis: 47 in whom epilepsy was excluded by capturing a typical attack on video-electroencephalographic monitoring (VEEM), and 55 not diagnostically confirmed with VEEM. RESULTS: Asthma was reported in 26.5% of pseudoseizure patients, compared with 8.6% of the psychotic controls (chi(2) = 8.6; p = 0.003). Asthma was reported at similar rates in the VEEM confirmed (29.8%) and non-VEEM confirmed (23.6%) pseudoseizure subgroups. The significant excess of reported asthma held for both the VEEM confirmed subjects (Pearson's chi(2) = 5.4, p = 0.02) and non-VEEM confirmed subjects (Pearson's chi(2) = 8.9, p = 0.003). CONCLUSIONS: There is an association between pseudoseizures and reported asthma. Various models are proposed whereby somatisation, anxiety hyperventilation, and dissociative elaboration may account for the observed association. Both asthma and anxiety hyperventilation may be important risk factors for the development of pseudoseizures. The reported asthma may itself be psychogenic in origin in a proportion of patients. Confirmatory prospective studies are indicated.

Schizophrenia-like psychosis arising de novo following a temporal lobectomy: timing and risk factors.

OBJECTIVES: To clarify risk factors for the development of schizophrenia-like psychotic disorders following temporal lobectomy, and to explore the possibility that the early postoperative period is a time of high risk for the onset of such chronic psychotic disorders. METHODS: Patients who developed schizophrenia-like psychosis were identified from a series of 320 patients who had a temporal lobectomy for medically intractable epilepsy. The relationship of their disorders to both the operation and subsequent seizure activity was examined. Using a retrospective case-control design, risk factors for the development of schizophrenia-like psychosis were established. RESULTS: Eleven patients who developed schizophrenia-like psychosis postoperatively were identified and compared with 33 control subjects who remained free of psychosis postoperatively. The onset of de novo psychotic symptoms was typically in the first year following the operation. No clear relationship between postoperative seizure activity and fluctuations in psychotic symptoms emerged. Compared with the controls, patients who become psychotic had more preoperative bilateral electroencephalogram (EEG) abnormalities, pathologies other than mesial temporal sclerosis in the excised lobe and a smaller amygdala on the unoperated side. CONCLUSIONS: Temporal lobectomy for medically intractable epilepsy may precipitate a schizophrenia-like psychosis. Patients with bilateral functional and structural abnormalities, particularly of the amygdala, may be at particular risk for the development of such psychoses.