Dual brain pathology in patients with affective aggressive episodes.
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Biomedical subjects
Publications and source records attributed to M R Trimble.
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OBJECTIVE: This is the first study to investigate the Quality of Life (QOL) of patients with Gilles de la Tourette's Syndrome (GTS). METHOD: One hundred and three out-patients with GTS completed a semi-structured interview and 90 of these completed questionnaires screening for depression, anxiety and obsessive-compulsive behaviour. QOL was measured with the SF-36 and the Quality of Life Assessment Schedule (QOLAS). RESULTS: Patients with GTS showed significantly worse QOL than a general population sample. They had better QOL than patients with intractable epilepsy as measured by the QOLAS, although the SF-36 showed significant differences on the subscales Role Limitation due to physical problems and Social Functioning only. Factors influencing QOL domains were employment status, tic severity, obsessive-compulsive behaviour, anxiety and depression. CONCLUSION: QOL is impaired in patients with GTS. Measurement of QOL could be used alongside conventional measurements to assess benefit of treatment. We recommend the QOLAS and SF-36 be used.
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The amygdala are thought to play an important role in emotional information processing. First studies indicate a link between amygdala atrophy, fear and aggression and between amygdala hypertrophy and depression. To investigate a possible relationship between amygdala volumes, aggression and depression, we measured the amygdala of 62 patients with temporal lobe epilepsy (TLE) with and without aggressive behavior or depression and 20 healthy volunteers using quantitative magnetic resonance imaging (MRI). Amygdala volumes of female patients (n=26) were significantly larger than those of males (n=36) (left side: P=0.001; right side P=0.05). Depressed patients displayed significant enlargement of both amygdala (left side: P=0.008; right side: P=0.001) There was no significant finding relating to the factor aggression neither was there any significant interaction between aggression, dysthymia and gender.
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This article deals with disorders of mood and the interaction between mood and cognitive function. The various ways in which environmental toxins can lead to disorders of mood are presented, and discussions regarding the neurobiology of mood are presented.
The aim of this work was to assess the health-related quality of life (HRQL) of patients pre and post surgical treatment for epilepsy. A total of 145 patients were interviewed during their pre-surgical assessment on the telemetry unit, Queen Square. The HRQL assessment comprised the quality of life assessment schedule (QOLAS), the EuroQol EQ-5D and the epilepsy surgery inventory (ESI-55). A total of 40 patients were followed up, of which 22 had undergone surgery and achieved 75% or greater reduction in seizures. The QOLAS scores for the patients who achieved 75% or greater seizure reduction post-op were significantly lower (i.e. improved HRQL) compared to baseline. The descriptive data suggest that the EQ-5D may not be capturing all of the QOL issues of relevance to patients with chronic, intractable epilepsy and the EQ-5D may not be valid for this group. Most patients queried the visual analogue scale (VAS) which asks for an overall rating of the respondent's self-perceived health. The most frequent comments, from 42% of patients, was that 'health' did not include their epilepsy. Despite this, the group whose seizures were reduced had significantly higher VAS scores at follow-up. We can conclude that the VAS is sensitive to clinical change. The baseline EQ-5D utility and follow-up scores were compared. There were no significant changes in QOL scores for either group. The patients who achieved 75% or greater reduction in seizures post-op scored significantly higher (i.e. better QOL) on 2/3 composite scores of the ESI-55 at follow-up. The QOLAS, the EQ-5D VAS and the ESI-55 were sensitive to clinically defined outcome. The results for the EQ-5D profile and the EQ-5D utility suggest that the EQ-5D is not a valid and responsive instrument for use in patients with intractable epilepsy.
The purpose of this paper is to understand the association between antiepileptic drugs (AEDs), patient characteristics, changes in seizure pattern and emergent psychiatric disorder, i.e. psychosis or affective disorder. To this end we carried out a retrospective casenote study on 89 patients who developed psychiatric symptoms during treatment with topiramate, vigabatrin or tiagabine. The psychiatric problem was either an affective or a psychotic disorder (not including affective psychoses). It was discovered that 99% of the patients suffered from complex partial seizures with or without secondary generalization. More than half were on polytherapy with two or more other AEDs. Nearly two-thirds had a previous psychiatric history. There was a strong association between the type of previous psychiatric illness and the type of emerging psychiatric problem, both for psychoses and for affective disorders. Patients on vigabatrin had an earlier onset of epilepsy and more neurological abnormalities than those on topiramate. Those patients on lower doses had a shorter interval between the start of the AED therapy and the onset of the psychiatric problem. A seizure-free period was observed in more than half of the patients before they developed the psychiatric symptoms, and of these more were likely to develop a psychosis rather than an affective disorder. There seemed to be an association of suppression of right-sided seizures and the onset of the psychiatric problem. The conclusions drawn were that patients with a previous history of psychosis or affective disorder tended to develop the same psychiatric problem with new AEDs. Those with a seizure-free period before the onset of the psychiatric problem were more likely to develop a psychosis than an affective disorder.
Recurrent episodes with interictal affective aggression are a rare but well-recognized problem in patients with temporal lobe epilepsy. They are referred to as episodic dyscontrol or, more precisely, as intermittent explosive disorder (IED). The amygdala play a crucial role in the affective evaluation of multimodal sensory input and the neurobiological mediation of aggressive behaviour. With hippocampal sclerosis, in the context of mesial temporal lobe sclerosis, being the most common cause of temporal lobe epilepsy, we hypothesized that the amygdala might be affected by the same pathogenic process in aggressive patients. We investigated 50 patients with temporal lobe epilepsy: 25 with and 25 without a history of IED. Data from clinical, electrophysiological, neuropsychological and psychometric investigations were obtained, as well as MRI scans for the quantitative assessment of possible amygdala pathology. We found no evidence of a higher prevalence of amygdala sclerosis in the aggressive patients. Hippocampal sclerosis was significantly less common in patients with temporal lobe epilepsy and IED. However, a significant subgroup of patients (20%) with temporal lobe epilepsy and aggressive behaviour had severe amygdala atrophy in the context of a history of encephalitis. Another subgroup of aggressive patients (28%) had different left temporal lesions affecting either the amygdala or periamygdaloid structures. IED was associated with left-sided or bilateral EEG and MRI abnormalities, low IQ and high scores in depression and anxiety.
PURPOSE: The occurrence of psychiatric symptoms after temporal lobectomy is well documented. The aim of the present study was to identify preoperative factors that predict postoperative psychiatric outcome. METHODS: We studied the case notes of 121 patients (from an initial sample of 167) who underwent temporal lobectomy at the National Hospital of Neurology and Neurosurgery, Queen Square, London, between 1988 and 1997. Data concerning gender, laterality of lesion, pathology, seizure outcome, psychiatric history, psychiatric outcome, resection volume, telemetry, and MRI scans were systematically collected. Factors that predict the occurrence of postoperative psychiatric symptomatology were investigated using correlational, chi(2), and logistic regression techniques. RESULTS: Poor postoperative psychiatric outcome in general was positively associated with preoperative bilateral independent spike discharges at telemetry. The size of surgical resection was positively correlated with the occurrence of postoperative emotional lability. The laterality of the epileptogenic lesion was not associated with a poor psychiatric outcome. Developmental lesions were associated with a good psychiatric outcome at a marginally significant level. Patients with a preoperative psychiatric history and de novo psychiatric symptomatology had a poorer surgical outcome in terms of seizure frequency, also at a marginally significant level. A significant correlation was found between a past psychiatric history and seizure outcome. CONCLUSIONS: We identified a high frequency of psychiatric symptoms both before and after temporal lobectomy, demonstrating that it is not a benign procedure from the point of view of psychopathology. Our results show that there are certain predictive factors that may help identify patients most at risk for postoperative psychiatric disorders.
BACKGROUND: Interictal episodes of aggression are often reported in patients with epilepsy. Some have characteristics of what has been referred to as episodic dyscontrol or intermittent explosive disorder (IED). Although structural brain abnormalities are thought to play a part in the pathophysiology of aggression, there are few in vivo studies of structural cerebral changes in patients with epilepsy and aggression. Using quantitative MRI, subtle structural brain abnormalities can be investigated in subgroups of patients with both epilepsy and episodes of affective aggression. METHODS: After automated segmentation of cerebral grey matter from T1 weighted MRI, the objective technique of statistical parametric mapping (SPM) was applied to the analysis of 35 control subjects, 24 patients with temporal lobe epilepsy (TLE) with a history of repeated, interictal episodes of aggression, and 24 patients with TLE without episodes of aggression. Both TLE patient groups were compared with each other and with the control subjects on a voxel by voxel basis for increases and decreases of grey matter. RESULTS: The patients with TLE with aggressive episodes had a decrease of grey matter, most markedly in the left frontal lobe, compared with the control group and with patients with TLE without aggressive episodes. CONCLUSION: These findings suggest that a reduction of frontal neocortical grey matter might underly the pathophysiology of aggression in TLE. These voxel by voxel comparisons can guide further in vivo studies into aggression.
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In this manuscript the life and times of the poet, Charles Lloyd are reviewed. In particular attention is paid to his seizures, and the development of what was probably an epileptic-related psychosis. It is pointed out how the development of the psychosis essentially destroyed his poetic career, and his life is set alongside theories of creativity and mental illness, as has been reviewed recently in the literature. It is suggested that while there may be links between creativity and bipolar disorder, sadly epilepsy is probably destructive to the creative writing process, particularly the writing of poetry.
BACKGROUND: Previous studies indicated an important role of the amygdala for emotional information processing. We investigated a possible relationship between amygdala volumes, aggressive behavior, and dysthymia, in patients with temporal lobe epilepsy (TLE). METHODS: Patients with TLE with and without aggression or dysthymia and healthy volunteers were assessed using quantitative MRI. Amygdala volumes were measured in a blinded fashion and corrected for total brain volumes. RESULTS: There was a highly significant enlargement of left and right amygdala volumes in patients with dysthymia (right side, p < .000; left side, p = .001). We found a significant positive correlation between left amygdala volumes (p = .02) and a trend towards positive correlation between right amygdala volumes and depression (p = .06), as measured with the Beck Depression Inventory. Amygdala volumes of females were significantly larger than those of males (left side: p = .005; right side: p = .06). CONCLUSIONS: This is the second report of a relationship between amygdala volumes and depressed mood, confirming an earlier finding in patients with bipolar disease, and the first study reporting a correlation between amygdala volumes and depression. Increased processing of emotional information might increase amygdala blood flow and subsequently, result in amygdala enlargement.
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In this paper, we have first reviewed the animal studies which suggest an association between the amygdala and aggressive behavior. This is followed by a review of the literature of aggression in epilepsy, emphasizing the less controversial peri-ictal aggressions, with the more controversial assertion that temporal lobe epilepsy in particular is associated with an increase in interictal aggression. We then go on to describe the results of some investigations using the MRI to examine amygdala pathology in a group of patients presenting with affective aggression in comparison with a control group. The main findings are that the patients with aggression tend to have lower IQs and more psychopathology than the control group. There is no difference in amygdala T2 and volumetric assessments between the groups, but a subgroup of patients are defined with aggression, left-sided amygdala atrophy, and a history of encephalitis.
BACKGROUND: In a retrospective study we investigated the role of social and biological risk factors for the development of major depression and schizophreniform psychoses in epilepsy. We tested the hypotheses that social risk factors are associated with depression and biological risk factors are associated with schizophreniform psychoses. METHOD: We studied 25 patients with epilepsy and paranoid-hallucinatory psychosis, 25 patients with epilepsy and major depression, and 50 non-psychiatric epilepsy patients (controls) with respect to biological and psychosocial variables. RESULTS: Schizophrenic patients had an earlier age of onset of epilepsy and a more severe epilepsy as characterised by history of status epilepticus, multiple seizure types and severity of seizures compared to non-psychiatric controls. Simple seizure symptoms were often vegetative and EEGs showed various abnormalities including temporal lobe discharges but no lateralisation to either side. With respect to antiepileptic drugs (AED) there were only few significant differences between groups: Polytherapy as well as treatment with phenytoin (DPH) was more frequent in psychotic patients as compared to non-psychiatric patients. Patients with psychoses were also characterized by a disturbed familial background, lack of interpersonal relationships, social dependency and professional failure. Depressive patients were significantly older than non-psychiatric controls and they suffered more frequently from focal epilepsies arising from the temporal lobe. They did not differ from controls with respect to severity of epilepsy. Treatment with valproate (VPA) was inversely linked with depression, suggesting that VPA may have prophylactic antidepressive properties in epilepsy patients. There were no psychosocial variables significantly linked with depression. CONCLUSIONS: In this study, patients with different forms of psychiatric complications in epilepsy could clearly be distinguished from controls. However, we could not confirm the simple hypothesis that there are biological predictors for schizophreniform psychoses and psychosocial predictors for major depression. Neurological and sociological variables seem linked with both, suggesting a multifactorial etiology.
The objective of this study was to compare the relative cost-effectiveness of two AEDs by a prospective clinical audit. Patients starting on the adjunctive therapies lamotrigine and topiramate were recruited from the out-patient epilepsy clinics at Queen Square. Three interview were scheduled: baseline; three months follow-up and six months from baseline. Of the 81 patients recruited, a total of 73 patients completed all three interviews. An intention to treat analysis was performed on the data. Seizure severity and frequency were assessed using the National Hospital Seizure Severity Scale. Side-effects, adverse events and reasons for stopping medication were also recorded. At the third interview, a total of 47/73 (64%) were still on the prescribed adjunctive drug. Outcome was assessed by two methods: the > 50% seizure reduction cited in the literature and a more stringent assessment of patient 'satisfaction' which we defined operationally on clinical criteria. Using this definition, a total of 10/73 (14%) patients were 'satisfied'. The relative costs of starting patients on each of the two AEDs were calculated, both drug costs and the costs of adverse events (the latter were defined as events requiring urgent medical attention). The costs of the two drugs were compared. A number of methodological issues relating to cost comparison are discussed. Outcome and pharmaco-economic studies need to assess more than reduction in number of seizures. They should take into account variables important for quality of life including side-effects and adverse events.