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N. Wood. Institute of Neurology, University of London, London, UK
Parkinson's disease (PD) is a common and incurable neurodegenerative disease. The genetic bases of genetically “simple” forms of PD is rapidly being solve. In the last few years, five genes have been unequivocally shown to cause PD. These are α‐synuclein, Parkin, LRRK2, PINK1 and DJ‐1. It is now clear that nigral cell loss and the specific clinical and pathological phenotypes seen in PD can arise through a number of different genetic (and presumably molecular) mechanisms. What is much less clear is whether there are several independent pathways or whether there is convergence of the molecular events. The finding of such genetic factors provides a very solid base from which to work to form towards a deeper understanding of the causes of cell dysfunction and death. Complete knowledge of these gene functions remains elusive. Recent work implicates abnormal protein accumulation, mitochondrial dysfunction and oxidative stress as common pathways to PD pathology. Combined proteomic, cellular and in vivo modelling is required to generate and investigate these pathways but the ultimate and most difficult task is to show the relevance of these events in human disease.
C. E. Clarke. University of Birmingham, Birmingham, UK
This presentation uses an evidenced based approach to summarise recent developments in the drug treatment of Parkinson's disease (PD) with emphasis on new agents and novel administration routes. This will include some non‐motor features such as dementia and psychosis.
Rotigotine is a non‐ergot dopamine agonist. It is lipid soluble and therefore it has been developed as a transdermal delivery system (patch) which produces stable 24 h stimulation from one application. Continuous dopaminergic stimulation may prevent or reverse motor complications. Rotigotine has been shown to be effective in two phase 2 and 3 placebo controlled trials. One phase 3 trial suggested that the current licensed maximum dose of rotigotine of 8 mg/day is equivalent to 12 mg/day of ropinirole. Side effects include nausea, vomiting and somnolence, but these are comparable with other oral dopamine agonists. Application site reactions occur in 37% of cases but do not often require withdrawal.
The symptomatic effects of the new monoamine oxidase type B (MAOB) inhibitor rasagiline in early PD are small but comparable with those seen with levodopa in the ELLDOPA trial.
Which is the most cost effective and safe drug class in early PD (levodopa, dopamine agonist or MAOB inhibitor) is still not known but is the subject of the ongoing PD MED Trial.
The Cochrane review of adjuvant catechol‐O‐methyl transferase (COMT) inhibitors versus placebo trials raised the possibility that the recently reintroduced tolcapone is more effective than entacapone in reducing off time and levodopa dose, but at the expense of more dyskinesia and dopaminergic adverse events. However, which is the most cost effective and safe adjuvant drug class in later PD (COMT inhibitor, dopamine agonist or MAOB inhibitor) is still not known, but is the subject of the ongoing PD MED Trial.
Amantadine has recently been found to have an antidyskinetic effect in four small randomised controlled trials (total patients=93).
Small trials have shown that most of the new atypical antipsychotics are either ineffective for psychosis in PD or cause deterioration in motor function. However, several trials have shown that clozapine is effective in PD psychosis and that it does not adversely affect motor function. It is licensed for use in PD with appropriate blood monitoring.
One large and several small trials have shown that the cholinesterase inhibitor rivastigmine can improve cognition and psychotic symptoms in PD dementia. The results of a large trial with donepezil are awaited. Further evidence of the cost effectiveness of this drug class in PD dementia is required.
R. Brown. King's College London, London, UK
Symptoms of depression occur in one‐third or more of patients with Parkinson's disease. These can be a source of distress and have a negative impact on several aspects of the life and function of the patient and their family. Despite its clinical significance, our understanding of the causes of depression remains poor. Clinically, identification is complex and treatment remains suboptimal because of the lack of acceptable clinical trial evidence. This presentation will review the evidence on the features of depression in Parkinson's disease and the possible contribution of both biological and social factors the in aetiology and maintenance. It will then cover some aspects of clinical management from identification to treatment, covering the potential roles of pharmacological and non‐pharmacological approaches.
Y. Agid. Fédération des Maladies du Système Nerveux, Centre d'Investigation Clinique 9503, Université Paris VI, CHU Pitié‐Salpêtrière, Paris, France
The basal ganglia in the human brain are considered to play a role in the selection and shaping of sensorimotor programmes and the automatic execution of learned motor plans. However, the basal ganglia are composed not only of sensorimotor territories but also associative and limbic territories, and are characterised by four main features: segregation of neuronal circuits; convergence of information; close interrelationships with the cerebral cortex; and complex interactions between the different cortico‐subcortico‐cortical neuronal loops. Therefore, it is hypothesised that the basal ganglia are also involved in the control of intellectual and psychic functions underlying the associative‐limbic areas within these structures. There are two ways to study the role of the basal ganglia in the control of intellectual and psychic functions in humans, whether normal subjects or patients: one way is to look at the activated or deactivated brain areas using functional neuroimaging in subjects who are confronted with various types of emotions. Another approach is to modify the activity of the basal ganglia neuronal circuits to see if one can reproduce these emotions. Several examples using neuroimaging and deep brain stimulation will be provided to demonstrate that phylogenetically ancient structures, such as the basal ganglia, are directly involved in the subconscious processing of emotions in normal subjects or of psychic disturbances in patients with neuropsychiatric disorders.
D. R. Weinberger. National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA
The search for schizophrenia susceptibility genes is arguably one of the more successful efforts in complex medical genetics. The genes tell us what the disorder is at a basic cellular level. The current evidence converges on subtle molecular bottlenecks in diverse aspects of synaptic processing and brain development. The discovery of schizophrenia susceptibility genes will enable the discovery of novel approaches to treatment, based on gene pathways and networks and the characterisation of risk phenotypes and the cellular and systems levels. The development of therapies derived from susceptibility genes will require deep understanding of genetic variation, gene processing, molecular pathways and the interacting environment. It is premature to assume that functional variants will or will not be found, that differing alleles and haplotypes suggest failure of replication and that pathogenic pathways will be too complex to be resolved. Current evidence suggests that allelic heterogeneity and novel RNA transcripts will be the rule for schizophrenia susceptibility genes. Unexpected therapeutic targets may emerge from cell models based on human genetic risk architecture. Therapeutic advances may emerge from targeting phenotypes related to abnormal cortical signal to noise.
F. Gilliam. Columbia University Medical Center, New York, NY, USA
Numerous epidemiological studies have identified increased rates of unipolar depression, psychosis and bipolar disorder in persons with epilepsy. Furthermore, recent case control and prospective incidence studies indicate that depression and suicidal ideation are risk factors for the later development of unprovoked seizures. Of the psychiatric disorders, depression appears to be most strongly associated with epilepsy, and emerging evidence suggests that depression is more closely associated with specific types of brain dysfunction than the social and vocational disability that commonly occurs with recurrent seizures. Papez initial description of the “emotional circuit” extending from the hippocampus to the cingulate gyrus, subcallosal gyrus and subcortical structures provides potential insight into the occurrence of mood disorders in epilepsy, especially his emphasis on the emotional disturbance that occurs with the convulsive effects of negri body incursion of the hippocampus in rabies. More recent studies suggest that neuroimaging markers of hippocampal hyperexcitibility, such as N‐acetyl aspartate, correlate with severity of depressive symptoms in temporal lobe epilepsy. These findings in conjunction with the observation of interictal activation of Brodmann's Area 25 with fluorodeoxyglucose‐positron emission tomography in depressed patients with mesial temporal lobe epilepsy invokes the hypothesis that depression in temporal lobe epilepsy is a unique neuropsychiatric syndrome arising from specific “epileptic” dysfunction of the limbic system. Identification of such a specific entity has important implications for further research and improvement in clinical care.
D. Chadwick. School of Clinical Science, University of Liverpool, Liverpool, UK
There is an ever increasing choice of antiepileptic drugs (AEDs), but little in the way of new information and evidence to support their optimal clinical use. In 1999 the National Health Service R&D Health Technology Assessment programme commissioned a large pragmatic randomised clinical trial to compare the clinical effectiveness, quality of life and health economic outcomes of standard and new AEDs. This has now been completed and the results will be presented. They indicate that lamotrigine may now represent a satisfactory alternative to carbamazepine for the treatment of focal seizures, while valproate remains the most effective treatment for generalised or unclassified epilepsy.
L. H. Goldstein. Institute of Psychiatry, London, UK
The diagnosis and management of patients with psychogenic non‐epileptic seizures (also referred to by our group as dissociative seizures) pose a significant challenge to those involved in the care of patients with epilepsy and related neuropsychiatric disorders. While diagnosis places considerable weight on the use of video‐EEG telemetry, management requires detailed understanding of the factors that may be of aetiological significance in the disorder as well as psychological/psychiatric comorbidities that may accompany it and factors that may serve to maintain it. The current talk will consider the range of comorbid psychiatric/psychological disorders that have been found in this patient group and, in particular, studies that consider the role of trauma and abuse and family dysfunction in the development of this disorder, as well as recent work that considers the role of anxiety and dissociation in its development and maintenance. The possibility of different aetiological models for this patient group will be considered. Given the importance of effective management of these patients, the literature on the treatment of non‐epileptic seizures will be reviewed.
M. Stephens. Finers Stephens Innocent, London, UK
Epilepsy affects approximately 6 million people across Europe—a significant proportion of the total 50 million disabled people in the region. Over the last 5 or so years, governments and legislators have shown an increasing willingness to implement regulations that actively promote and protect the rights of these people. Already a range of legal strategies have been adopted, both internationally and nationally, to achieve equality for disabled people and facilitate their inclusion into mainstream society in Europe. This has been done primarily through anti‐discrimination law but there is also a human rights framework in Europe which can and is being used to ensure that the disabled are not disadvantaged.
C. Warlow. University of Edinburgh, Edinburgh, UK
It is a strange paradox that neurologists and psychiatrists share the same organ but not the same wards, or even often the same hospitals. It is another paradox that so much of the “psychiatry” encountered in general hospitals is not what most psychiatrists have to do with, or what many medical students are taught—it is neither schizophrenia nor bipolar disorder, but the myriad of patients with emotional and psychological consequences of organic disease, and others who have symptoms but no disease (sometimes called somatisation). There are far too many of these “somatisers” to be treated by psychiatrists; they have to be managed by other specialists and general practitioners. But, and here is another paradox, as medicine fractionates into ever smaller compartments, and GPs work more and more part time, this is not thought of as anyone's business. It must be time for a rethink about how students should engage more with patients who have symptoms unexplained by disease, but that will require more engagement from neurologists and other specialists. Liaison psychiatrists have a key role in working with neurologists, but they cannot be expected to see all patients.
J. LeDoux. Center for Neural Science and Department of Psychology, New York University, New York, NY, USA
Fear and anxiety are normal adaptive functions of the brain. However, millions of people suffer from disorders involving excess or inappropriate fear and anxiety. Included are phobic, panic, post‐traumatic stress, generalised anxiety and obsessive compulsive disorder. Research on the brain mechanisms of fear and anxiety gives us clues about how these normally function, what changes in the brain when they malfunction and how specific malfunctions might be most effectively treated. Better control of inappropriate and excess fear and anxiety would improve health and well being, both for individuals and societies.
A. Grayling. Birkbeck College, University of London, London, UK
Humankind is a puzzle to itself in many ways, not least in connection with the question of what can be meant by the expression “human nature”. Is there one specifiable such thing, whose essence we can capture, or is human nature contingent and variable? If it is possible to give a general characterisation of something that answers to the expression, where should we seek the best set of concepts to describe it: history, anthropology, psychology, philosophy, biology—even the arts and literature—or all of them? Can we learn something deeply revealing about humanity by examining its closest primate relatives? Does what we learn by studying humanity's cultures, moralities and institutions trump what biology can tell us, or does the possibility exist for a genuinely informative synthesis? In this lecture I consider what kind of theory a theory of human nature might be, and what resources it would best draw upon in the heroic endeavour to investigate what Alexander Pope said is man's proper study.
M. Cuddy, B. Papps, M. Thambisetty, P. N. Leigh, L. H. Goldstein. Institute of Psychiatry, London, UK; email@example.com
AimsChanges in memory for and processing of emotionally salient material have been reported in individuals with amyotrophic lateral sclerosis (ALS). It is not known whether these changes are related to the lower than expected prevalence of depression reported in this population. This study aimed to replicate and extend the finding of Papps et al (2005), and to investigate the relationship between emotional memory (EM) performance and self‐reported depression.
Methods19 patients with ALS and 19 matched controls were assessed using neuropsychological tests and questionnaires.
ResultsPatients with ALS and controls did not differ significantly in their EM performance. However, examination of percentile scores revealed that a significantly larger proportion of patients with ALS than controls performed poorly on measures of recall and recognition of emotionally salient words. A significant association between self‐reported depression and some measures of EM was found in control participants but not in patients with ALS.
ConclusionsThe results suggest that a subgroup of patients with ALS may show changes in EM. Furthermore, the finding that patients did not show the normative relationship between EM scores and depression scores suggests that EM may be mediated differently in patients with ALS.
J. L. Drakeford, N. M. J. Edelstyn, F. Oyebode, W. R. Calthorpe, S. Srivastava, T. Mukherjee. School of Psychology, University of Keele, Keele, Staffordshire, UK; firstname.lastname@example.org
AimsTo determine whether major depressive disorder (MDD) gives rise to deficient recognition of neutral faces.
Methods18 patients with MDD, according to DSM IV criteria, and 24 healthy volunteers were recruited. Patients were in remission during the study. Participants were required to discriminate 50 target faces (black and white photographs of male faces with neutral expressions), exposed for 3000 ms during a study phase, from 50 novel distracter faces introduced during the test phase. For all positive identifications (target hits as well as distracter false alarms) made during the test phase, participants indicated whether these were based on recollection of the face having been presented earlier, or limited to feelings of knowing/familiarity occurring in the absence of recollection.
ResultsThe results were analysed in terms of overall recognition of faces using the signal detection measure d prime (d′), recollection rates (hit rate minus false alarm rate) and familiarity (d′). The MDD group was significantly impaired on measures of facial recognition memory (F=15.05, p<0.001) and familiarity driven recognition decisions (F=14.66, p<0.001). Recollection rates also approached significance (F=3.93, p=0.054).
ConclusionsThese findings suggest that MDD is not limited to only deficits in recognition of facial emotion cues, but also extends to recognition memory for neutral faces. Furthermore, this memory impairment is most evident in the processes which subserve feelings of familiarity. An abnormality in the subjective experience of familiarity may have clinical implications for patients' reports of derealisation and depersonalisation. These findings also suggest that patients with MDD have impairments in familiarity driven recognition even when apparently recovered from an episode of illness.
M. Reuber, M. Schwabe, S. J. Howell. Academic Neurology Unit, Royal Hallamshire Hospital, Sheffield, UK; email@example.com
AimsTo explore whether features thought to be helpful in the differentiation of communication behaviour of German speaking patients with epileptic or non‐epileptic seizures (NES) could be used to generate a diagnostic hypothesis of epilepsy or NES in English speakers.
MethodsFocused conversation analysis (CA) of transcripts of 11 clinical doctor–patient encounters with patients with video‐EEG proven epileptic or NES by a linguist blinded to medical tests and diagnosis.
ResultsThe linguistic and interactional criteria previously identified in German speakers were also detected in English patients. A correct diagnostic hypothesis of epilepsy or NES was made in all cases.
ConclusionsCA is a very promising tool in the diagnosis of seizure disorders. Further research is justified to assess sensitivity and specificity, and to enhance the clinical applicability of the method.
F. Lázaro‐Perlado1, A. Bajo2, S. Fleminger3. 1Grafton Manor, Grafton Regis, Northampton, UK; 2Brain Injury Rehabilitation Unit, Edgware Community Hospital, Edgware, Middlesex, UK; 3The Maudsley Hospital, London, UK
AimsThe current research project plans to study the effects of depression, anxiety and attentional disorder in the decision making process of a free choice recognition memory test, as measured by the Signal Detection Memory Test (SIGNAL), in a group of subjects with a history of acquired brain damage.
MethodsThis study is a retrospective case note review of 86 brain injured subjects. Two subgroups were identified: depressed (Beck Depression Inventory (BDI) score >19; n=20) and non‐depressed (BDI <20; n=66) brain injured subjects. Subjects were recruited from two tertiary centres for neuropsychological rehabilitation. Subjects had undertaken a computerised test battery which included SIGNAL and six other psychological scales (BDI, Cognitive Failures Questionnaire (CFQ), Questionnaire of Experiences of Dissociation (DIS), Maudsley Obsession–Compulsive Inventory (MOC), Zung's Anxiety Scale (ZG), Snaith's Irritability Scale (IRR)). We looked for differences between the two subgroups. Correlations between d′ (memory capacity), β (response bias), FAR (false alarm rate), CFQ (attentional disorder) and ZG (anxiety) were assessed within the depressed subgroup.
ResultsIn the total group there was a high prevalence of neuropsychiatric comorbidity. Within the depressed subgroup, there was a positive correlation between BDI and FAR. There were negative correlations between FAR and d′, β, ZG and CFQ.
ConclusionsThese findings indicate that brain injured survivors present high levels of neuropsychiatric disorders. Contrary to our clinical experience, depressed subjects were more liberal in their responses. It is unclear whether this is a direct consequence of the head injury, secondary to the neuropsychiatric comorbidity or a consequence of both.
Z. F. Falope, S. Deb, E. H. G. Rickards, T. P. Powell, P. Njoboro.
BackgroundDepression is common after acquired brain injury (ABI). Patients who are depressed have reduced motivation for rehabilitation, therefore assessment and treatment of depression is important. Assessment of depression relies on self‐report measures and diagnostic interviews. Few instruments are developed and validated in ABI and there is no consensus on cut‐off scores. The aim of the study is to compare the accuracy of Hospital Anxiety and Depression Scale (HADS) and Beck's Depression Inventory‐II (BDI‐II) in screening for depression after brain injury and to determine the most appropriate cut‐off points.
MethodsFifty consecutive outpatients (34 males and 16 females) with ABI predominantly traumatic brain injury and stroke completed HADS and BDI‐II followed by clinical interview for DSM IV criteria for depression used as the ‘gold standard'. The sensitivity, specificity, positive predictive and negative predictive values were calculated for different cut‐off points of HADS and BDI‐II and receiver operating characteristics (ROC) curves were obtained.
ResultsMost suitable cut‐off score for HADS‐depression subscale was 8/9 with a sensitivity of 90% and specificity of 69%. A high sensitivity and NPV were obtained at a cut‐off score of 5/6 or lower. The area under the ROC curve was 0.840. The most suitable cut‐off score for BDI‐II was 19/20 with sensitivity of 90% and specificity of 75%. A 100% sensitivity and NPV were obtained with cut‐off scores of 15/16 or lower. The area under the ROC curve was 0.878.
ConclusionsBoth HADS and BDI‐II proved to be satisfactory for screening for depression in outpatients with ABI. Both scales exhibited similar levels of sensitivity at the optimum cut‐of scores but BDI‐II had slightly higher specificity.
B. Ghosh, J. Langosch, S. Rand, S. Sharma, C. Tench, R. Stratton, D. D'Cruz, M. Trimble, G. Barrett, H. Ring. firstname.lastname@example.org
AimsTo determine the prevalence of lability among patients with systemic lupus erythematosus (SLE) and any association with event related potentials (ERPs).
MethodsThirty‐two consecutive attendees at an SLE clinic were recruited into the ethically approved study with consent. Anxiety, depression, lability and ERPs (Mismatch Negativity (MMN), N1, P3a, P3b) were measured.
Results15 patients had high lability (47%). The high lability group had higher anxiety. There were no significant differences in other variables. In the high lability group, MMN latency to peak response was significantly reduced at Fz and Cz, and N1 latencies to standard tones were reduced at Fz, F3 and F4. Results were unchanged by including anxiety as a covariate.
ConclusionsThis study showed that high lability was common in this cohort and that high lability correlated with reduced latencies in early pre‐attentive ERPs. Lability has been under investigated as a cause of psychopathology in SLE. Consistent clinical indicators of neuropathological lupus are rare and eliciting MMN and N1 may shed light on underlying pathophysiology.
N. A. Harrison, A. E. Cavanna, B. Draganski, M. M. Robertson, R. S. Frackowiack, H. D. Critchely. UCL, Institute of Cognitive Neuroscience, London, UK; email@example.com
BackgroundEchophenomena, including echopraxia (mimicry of motor behaviours), are common in Tourette syndrome (TS). Emotional empathy score in normal subjects is predicted by magnitude and rapidity of mimicry of facial expressions, measured using EMG. Recent functional MRI studies highlight activation of “mirror neuron” regions, concerned with processing socially meaningful information, during facial expression mimicry. We therefore used empathy questionnaires and structural neuroimaging to explore the empathetic style and neural correlates of echopraxia in TS.
HypothesisWe predicted that echopraxia positive (EP+) TS individuals would show higher trait empathy and exhibit greater grey matter volume in “mirror neuron” regions.
Methods70 consecutive individuals with TS were recruited from a specialist TS clinic. Echopraxia was assessed using a specifically targeted clinical interview (AC), including 24 specially developed echopraxia induction procedures. Subjects mirroring one or more actions were labelled EP+. 47 of 70 subjects also underwent high contrast T1 weighted structural MRI neuroimaging. All subjects were assessed for emotional and cognitive empathy (Davis Interpersonal Reactivity Index), tic severity (Yale Global Tic Severity Scale), depression (Beck Depression Inventory), obsessive–compulsive symptoms (Leyton Obsessional Inventory) and anxiety (State‐Trait Anxiety Inventory).
Results30 subjects (43%) were EP+. EP+ subjects scored significantly higher than EP− subjects on Davis subscales of empathic concern (p=0.01), personal distress (p=0.03) and fantasy scores (p=0.02). Neuroimaging revealed EP+ subjects to have greater grey matter volumes in the left fronto‐parietal “mirror neuron” and postero‐medial parietal cortex.
ConclusionsEchopraxia in TS is associated with enhanced empathetic concern and corresponding increased brain volume within “mirror” and “default mode” systems, supporting cognitive processes related to both internal and external aspects of self and other.
S. B. Harvey, M. Wadsworth, S. Wessely, M. Hotopf. Department of Psychological Medicine, Institute of Psychiatry, Weston Education Centre, London, UK; firstname.lastname@example.org
AimsIncreased rates of psychiatric disorder have previously been reported in those diagnosed with chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME). We aimed to test the hypothesis that individuals with self‐reported CFS/ME have increased rates of psychiatric disorder prior to the onset of their fatigue symptoms.
Methods5362 participants were prospectively followed with various measures of personality, psychiatric disorder and energy levels collected over the first 43 years of their life. CFS/ME was identified through self‐report during a semistructured interview at age 53 years.
ResultsThose with a psychiatric disorder between the ages of 15 and 36 years reported increased rates of CFS/ME later in life, with an odds ratio (adjusted for sex) of 2.62 (95% confidence interval 1.25 to 5.51; p=0.01). Increased levels of psychiatric illness, in particular depression and anxiety, were present prior to the occurrence of fatigue symptoms. There was a dose–response relationship between the severity of psychiatric symptoms and the likelihood of later CFS/ME. Personality factors were not associated with a self‐reported diagnosis of CFS/ME.
ConclusionsThis temporal, dose–response relationship suggests that psychiatric disorders, or shared risk factors for psychiatric disorders, are likely to have a role in the aetiology of CFS/ME.
R. Kanaan, T. Craig, S. Wessely, A. David. Institute of Psychiatry, London, UK
ObjectivesConversion disorders comprise neurologically unexplained symptoms with a presumed psychiatric cause, although a neuroscientific basis for this is lacking. The standard psychiatric model of conversion is that events and processes which might explain the symptoms are either repressed or otherwise subconscious. This makes assessments based on subjective reports unreliable. We circumvent this by using a standardised method to quantify stressful life events and by assessing objectively the neural correlates of emotion processing.
MethodsSingle case study of a 37 year old woman with clinically repressed recall and unexplained right sided paralysis. We describe the application of the Life Events and Difficulties Schedule (LEDS) to her history, and a novel functional MRI procedure exploring emotion processing of traumatic and control memories.
ResultsWhile in the scanner, cued recall of the clinically repressed event was associated with regional brain activations characteristic of emotional arousal, including the amygdala and right inferior frontal lobe, when compared with an equally severe event from the patient's past, as rated by the LEDS. Such recall was also associated with decreased motor activity in the area corresponding to the subjectively paralysed limb.
ConclusionThis case study provides neuroimaging evidence for a connection between traumatic events and ongoing neurological symptoms.
C. R. Butler, K. S. Graham, J. R. Hodges, N. Kapur, J. M. Wardlaw, A. Zeman. Peninsula Medical School, Exeter, UK; email@example.com
AimsThis study was designed to study the clinical, neuropsychological and radiological features of Transient Epileptic Amnesia (TEA), an under‐recognised presentation of epilepsy in which transient amnesia is the principle manifestation of seizures.
Methods50 patients with TEA were recruited from across the UK. Clinical evaluation, neuropsychological testing and MRI of the brain were performed in cases and 24 matched controls. Voxel based morphometry (VBM) was used to identify focal cortical atrophy.
ResultsTEA develops in later life (mean onset 62 years). Amnesic episodes are frequent (median 12/year), brief (median duration 30–60 minutes) and often occur on waking (37/50 cases). Olfactory hallucinations occurred in 21 patients. Attacks ceased on anticonvulsant medication in 45/47 cases but 40/50 patients described persistent memory difficulties. Despite normal performance on standard memory tests, patients exhibited accelerated forgetting over 3 weeks (p<0.001) and loss of autobiographical memories for recent and remote events (p<0.001). VBM revealed cortical loss bilaterally in the medial temporal lobes that did not correlate with forgetting or autobiographical memory scores.
ConclusionsTEA is a distinctive epilepsy syndrome with characteristic clinical features. It is associated with accelerated forgetting and remote memory loss that may result directly from medial temporal lobe seizure activity.
S. Palazzi. Michael Rutter Centre, The Maudsley Hospital, London, UK; firstname.lastname@example.org
AimsTo describe the mental health symptoms of children with epilepsy referred to a Child and Adolescent Mental Health Services (CAMH) specialist setting; to compare children with epilepsy with other CNS disorders and without CNS disorders with regard to psychopathology and risk factors; to look at the interactions between psychosocial risk factors and psychopathology in children with epilepsy
MethodsThe sample includes children seen at the Maudsley Hospital National and Specialist CAMH Service between 1983 and 1991. There were 3508 valid records based on the Maudsley Item Sheet. Variables included psychological symptoms and social variables. An SPSS based algorithm was used to categorise patients in a multiaxial system and sort them into three subgroups: (1) children with epilepsy, (2) children with other CNS or genetic conditions and (3) others.
ResultsThe three subgroups had 189, 286 and 3039 patients, respectively. Externalising symptoms were more frequent in children with epilepsy than internalising symptoms. Children with epilepsy were more likely to present with psychotic symptoms and hyperkinetic manifestations than the other subgroups. Also, they had depression more frequently than subgroup 2, but less often than subgroup 3.
ConclusionsChildren with epilepsy appear to be referred to specialist mental health services for externalising rather than internalising behaviours.
U. C. Wieshmann, G. Hart, P. Eldridge, T. Varma. The Walton Centre for Neurology and Neurosurgery, Liverpool, UK; email@example.com
AimsThe aim of this study was to determine the frequency of early depression and anxiety in patients undergoing temporal lobectomies for refractory epilepsy.
MethodsPatients operated on for refractory temporal lobe epilepsy between 2004 and 2006 were included. Exclusion criteria were extratemporal epilepsy and the presence of a glioma.
Results27 patients were included (11 female, 16 male), mean age 32.5 years (range 18.5–48.5 years). 24 had hippocampal sclerosis or gliosis and 3 had caveromas. 12 had operations on the left and 15 on the right side. 3 had early postoperative convulsions and 1 continued to have habitual seizures, although less frequently. 9 patients (33%) had marked affective disturbances after surgery (5 were female and 4 were male). 6 patients experienced depression, 1 took an overdose of paracetamol and 1 was found to be intoxicated with carbamazepine in the context of a possible overdose. 3 patients suffered anxiety (1 had early postoperative seizures). In all patients the symptoms occurred in the weeks after discharge and improved spontaneously.
ConclusionsAffective disturbances were detected in one‐third of all patients undergoing temporal lobectomies. The true prevalence may be higher. Affective disturbances occurred in seizure free patients and affected both men and women.
M. Yogarajah, H. W. R. Powell, G. J. M. Parker, D. C. Alexander, M. R. Symms, P. Boulby, C. A. Wheeler‐Kingshott, G. J. Barker, M. J. Koepp, J. S. Duncan. National Society for Epilepsy, MRI Unit, Bucks, UK; firstname.lastname@example.org
AimsTemporal lobe epilepsy (TLE) is associated with disrupted memory function, and memory impairment is common following anterior temporal lobe resection. The structural abnormalities underlying this have not been demonstrated previously, and may assist surgical planning to minimise deficits.
MethodsWe performed magnetic resonance tractography in 18 patients with unilateral TLE undergoing presurgical evaluation (8 left TLE, 10 right TLE), and in 10 healthy controls. A seed point in the anterior parahippocampal gyrus was selected to trace the white matter connections of the medial temporal lobe. Correlations were performed between volume and mean fractional anisotropy (FA) of the connections, and preoperative and postoperative memory performance.
ResultsThere was no significant difference between the left and right sided connections in controls. In the left TLE patients, connections ipsilateral to the epileptogenic region were found to be significantly reduced in volume and mean FA compared with the contralateral region. Significant correlations were found in left TLE patients between left and right FA, and verbal and non‐verbal memory, respectively.
ConclusionsTractography demonstrated the reorganisation of white matter pathways that may underlie impaired memory function in TLE. A detailed knowledge of the integrity of these connections may be useful in predicting memory decline following temporal lobe surgery.
P. H. Clough, K. J. O'Driscoll. The David Lewis Centre for Epilepsy, Warford, Alderley Edge, Cheshire, UK
A 46‐year‐old male was charged with indecent assault. A previous charge of indecent exposure was abandoned in court because of non‐attendance of the key witness. A further arrest for indecent assault did not lead to charges after police interview.
From 29 years of age, the defendant had been investigated and treated for probable epilepsy. A provisional diagnosis of complex partial seizures was made and his attacks appeared to respond to carbamazepine. The diagnosis, however, remained in doubt. Events were witnessed by family and clinicians which included disinhibited behaviour deemed to be offensive. The victim, in the index event, also described similar behaviour. Certain features were consistent with oroalamentory and gestural epileptic automatisms.
The court was unimpressed with the defence of epileptic automatisms but reluctantly allowed adjournment for videotelemetry. The videotelemetry captured a seizure with right temporal lobe onset and secondary generalisation. There were associated epileptic automatisms similar to the behaviour with which the defendant was charged. The defendant was found not guilty by reason of insanity.
A. EugenioCavanna, C. Selai, A. Schrag, M. Orth, D. Morley, M. M. Robertson, H. D. Critchley. A.Cavanna@ion.ucl.ac.uk
AimGilles de la Tourette Syndrome (GTS) is a chronic neuropsychiatric disorder which has a significant detrimental impact on the health related quality of life (HR‐QOL) of patients. The aim of this study was to explore the main determinants of HR‐QOL in patients with GTS.
MethodsThe QOL of 82 consecutive patients attending the Tourette Clinic, National Hospital for Neurology and Neurosurgery, London, UK, was assessed using the EQ‐5D, a generic HR‐QOL tool, and the GTS‐QOL, a new 40 item GTS specific HR‐QOL questionnaire. Each patient was also evaluated using the GTS‐National Hospital Interview Schedule, the Yale Global Tic Severity Scale (YGTSS), the Spielberger State‐Trait Anxiety Inventory (STAI), the Beck Depression Inventory (BDI) and the Leyton Obsessional Inventory (LOI).
ResultsThe results of the generic EQ‐5D, compared with EQ‐5D data from a large UK general population study, showed that QOL was significantly impaired in this patient group. EQ‐5D and GTS‐QOL scores demonstrated satisfactory convergent validity (Spearman's rho=0.70; p<0.01). YGTSS, STAI, LOI and BDI scores all correlated significantly (p<0.01) and in the expected direction with GTS‐QOL scores.
ConclusionsThe QOL of patients with GTS is impaired compared with the general population. Tic severity, anxiety, depression and obsessionality seem to equally contribute to QOL perception. Specific instruments taking into account the complexity of the clinical picture of GTS, such as the GTS‐QOL, will prove useful in the assessment of the overall well being of this population.
J. C. Freeland, D. Todd, T. Heritage. email@example.com
AimsOnly a single case study of seasonal affective disorder following brain injury (Hunt and Silverstone, 1990) has been published to date. The current study explored two methods of assessing seasonal influences on a common affective symptom in acquired brain injury—irritability/aggression.
MethodsThe irritability/aggression recordings of clients from two neuro‐rehabilitation units in the UK were studied. In the multivariant approach, six clients with apparent seasonal patterns of irritability were chosen from a population of 27 clients based on visual analysis of their data. In an analysis of covariance, significant interaction between season and the irritability/aggression measure (F,(3,24)=8.513, p<0.05) was found. In the Fourier analysis technique, clients with at least 32 weeks of aggression recordings were studied. A fast Fourier analysis found 3 of 41 clients who displayed significantly higher levels of irritability/aggression in the power spectrum of 13 weeks (equinox–solstice interval).
ResultsThe incidence of irritability/aggression which was seasonally influenced using a visual analysis approach found a base rate of 22% and, using the more conservative Fourier analysis approach, found a 7% base rate.
ConclusionsSeasonal influences on irritability/aggression is an area which deserves greater consideration in the rehabilitation and treatment of persons with acquired brain injury.
S. D. Martin, E. Martin, A. Hildreth, M. Freeston, S. Thirumalai, A. Knight, D. Williams. firstname.lastname@example.org
AimsTo explore sequential patterns of D2/D3 receptor occupancy in patients treated with mirtazapine alone versus mirtazapine and interpersonal psychotherapy (IPT).
MethodsWe previously reported brain blood flow changes in the striatum with IPT for depression. In this study, 20 patients were randomised to two treatment groups and had blind clinical ratings and iodobenzamide‐single photon emission computed tomography (IBZM‐SPECT) at week 0 and week 6.
ResultsThere were significantly more clinical responders in the combined treatment group (psychotherapy and medication) than with medication alone. Thirty per cent of the 20 patients responded at 6 weeks. Responders by definition had a 40% reduction in Ham D from week 0 to week 6. Of the responders, 83% were receiving combined treatment. There were no D2/D3 differences between treatment groups or follow‐up. Females, agitated patients (all of whom stayed agitated throughout the study) and non‐responders all had higher D2/D3 receptors. Patterns of D2/D3 change and laterality varied with levels of treatment resistance.
ConclusionsIPT augmentation is important in treatment resistant depression (TRD). Excess D2/D3 striatal binding indicating receptor pathoplasticity may have been underemphasised in the aetiology of TRD. We suggest further research on D2/D3 antagonism in IPT augmentation for TRD.
The full paper of this project is under submission to Archives of General Psychiatry.
F. M. O'Brien, P. Devitt, K. Murphy. Department of Psychiatry, Beaumont Hospital/RCSI, Dublin, Ireland; email@example.com
AimsThis audit aimed to compare the number and pattern of referrals from neurosurgery and neurology specialist services to the liaison neuropsychiatry service for the years 2002 and 2005, and to examine trends over time. We also aimed to examine the results of subsequent psychiatric assessment and management of all patients seen on consult.
MethodsThe hospital patient information profile explorer computer program (PIPE) was accessed to determine the names and original consult referral data for the years 2002 and 2005. Collection of patient demographic data, medical history, results of psychiatric assessment, management and follow‐up were then obtained from patient charts, retrospectively. These data was then inputted into the SPSS statistical software program and relevant statistical analysis performed where necessary.
ResultsThe number of referrals to the neuropsychiatry service in Beaumont Hospital increased significantly between 2002 and 2005. Of the patients reviewed, epilepsy was the most common medical diagnosis and depression of moderate severity the most likely psychiatric diagnosis made. Furthermore, conversion disorder appears to be becoming more frequent. Antidepressants, principally selective serotonin reuptake inhibitors, are commonly prescribed. Follow‐up by neuropsychiatry outpatient services was becoming more frequent over time.
ConclusionsThe neuropsychiatry service within Beaumont Hospital performs a valuable function in helping to diagnose and treat mental health problems within a vulnerable patient population. This audit showed that the demands on the neuropsychiatry liaison service have been growing. Further resources should be allocated to expanding the number and range of inpatient and outpatient mental health services available to patients seen within this service, especially those relating to specialist neuropsychology and social work.
E. Szabadi, E. R. Samuels, R. H. Hou, R. W. Langley, C. M. Bradshaw. firstname.lastname@example.org
AimsD2 dopamine receptor agonists used in the treatment of Parkinson's disease cause sedation and nausea, and the nausea can be prevented by domperidone, a peripherally acting D2 receptor antagonist. It is assumed that domperidone does not reduce the therapeutic efficacy of a D2 receptor agonist. We examined the effects of the D2 receptor agonist pramipexole with and without domperidone coadministration on measures of D2 dopamine receptor activity inside (alertness, autonomic function) and outside (endocrine function) the blood–brain barrier.
Methods16 male volunteers participated in 4 weekly sessions (pramipexole 0.5 mg, domperidone 40 mg, their combination and placebo). Treatments were administered according to a balanced double blind design. Alertness (visual analogue scales), autonomic (pupil diameter and reflexes, blood pressure, heart rate, salivation, temperature) and endocrine (blood levels of prolactin, thyroid stimulating hormone, growth hormone) were assessed. Data were analysed with ANOVA.
ResultsPramipexole reduced alertness, light reflex amplitude and prolactin level, and increased pupil diameter, light reflex latency and growth hormone level. Domperidone increased prolactin and thyroid stimulating hormone levels, and attenuated the pupillary effects of pramipexole.
ConclusionsAttenuation of the central pupillary effects of pramipexole by domperidone indicates that domperidone can have access to central D2 dopamine receptors.
M. Koeda, M. Matsuura, H. Takahashi, Y. Okubo, H. Tanaka. email@example.com
BackgroundRecent neuroimaging studies have shown right temporal activation caused by human identity or emotional prosody as well as human voice perception. However, no study has reported on cerebral function in terms of insight into the inflexion of a person's greeting.
AimsWe aimed to investigate cerebral response while recognising the inflexion in speakers' voices.
MethodsTwo greetings, “Ohayo” and “Yha”, were prepared in Japanese. Initially, three types of greetings were selected: favourable (positive) greeting, unfavourable (negative) greeting and neutral greeting (neutral), by questioning 30 subjects. Using these classified greetings, 10 normal right‐handed subjects (5 men, 5 women) were scanned by functional MR imaging while they judged whether the speakers' voices were positive, negative, or neutral.
ResultsUnder the positive–neutral contrast, cerebral activation was observed at the bilateral superior and middle temporal gyrus, parahippocampus and anterior cingulate gyrus. Under the negative–neutral contrast, cerebral activation was revealed at the anterior middle temporal gyrus, superior temporal gyrus, fusiform gyrus, amygdala, parahippocampus and anterior cingulate gyrus in the right hemisphere.
ConclusionOur study indicates that recognition of the inflexion of speakers' voices is closely related to cortical–subcortical function, including the right temporal lobe and limbic system.
P. Wicks. firstname.lastname@example.org
Over the past decade, an increasing number of patients have used the internet as a static source of information about their condition. Patients with neurological conditions such as motor neurone disease, Parkinson's disease, multiple sclerosis and epilepsy are forming online communities based around interactive message boards or “forums”. These allow patients throughout the world to share information and personal experiences in a “safe” virtual environment, usually through sites set up by hospitals, charities or individual patients. Since 2004, a second wave of mainstream internet sites such as EBay, Flickr, MySpace, YouTube and Wikipedia have been launched, emphasising collaborative information sharing, under the title “Web 2.0”. Here we report a new website for patients with neurological conditions which allows them to share their experiences in the traditional way, but in addition contains sophisticated features for tracking their symptom severity, medication usage and use of assistive technology. The aims are threefold: firstly, to allow users to find a “patient like me” to ask questions or share advice; secondly, to empower patients to take a lead in managing their own condition by equipping them with tools to measure their symptom severity and highlight their needs during the neurological consultation; and thirdly, as a platform for research to rapidly access thousands of patients to conduct online studies.
S. Bhandari1, D. Samellas1, M. Lai2, G. F. Bottazzo3, E. Palazidou1. 1Department of Psychiatry, East London and The City University Mental HealthTrust, The Royal London Hospital (St Clement's), London, UK; 2Scientific Directorate, Ospedale Pediatrico Bambino Gesù, Scientific Institute (IRCCS), Rome, Italy
BackgroundLithium treatment in bipolar disorder is associated with thyroid hormone abnormalities, and a link with thyroid autoantibodies has been suggested.
AimsTo examine the extent of abnormalities of thyroid function, including the presence of thyroid autoantibodies in bipolar mood disorder, and to investigate a possible association with factors such as lithium exposure.
MethodsPlasma concentrations of thyroid stimulating hormone (TSH), T4 and thyroid autoantibodies were measured in 45 patients with a DSM‐IV diagnosis of bipolar mood disorder. A logistic regression model was used to examine factors predicting the presence of thyroid autoantibodies; predictor variables included sex, lithium exposure, history of autoimmune disease, duration of bipolar disorder and age.
Results7 of the 45 patients (15.6%, 95% CI 4.97 to 26.1) had abnormal serum T4 concentrations and 11 (24.5%, 95% CI 11.9 to 37.0) had abnormal TSH concentrations. 8 of the 45 patients (17.8%, 95%CI 6.6 to 29.0) had positive thyroid autoantibodies. A history of autoimmune disease was associated with the presence of thyroid autoantibodies (p=0.001, odds ratio=77.484, 95% CI 5.611 to 1070.020); no association was found between lithium exposure, sex, age or duration of bipolar mood disorder and the presence of autoantibodies.
ConclusionsThere is an increased prevalence of thyroid autoantibodies and thyroid hormone abnormalities in patients with bipolar mood disorder. The presence of thyroid autoantibodies is associated with a history of autoimmune disease but not with lithium treatment.
N. Ilankovic, V. Ilankovic, L. M. Ilankovic, A. Ilankovic, T. Lakovic. email@example.com
AimsFunctional assessment of parkinsonismus and other psychomotor disturbances in chronic psychotic patients and applying the special neurorehabilitation method VILAN.
MethodsFunctional diagnostic and measurement with clinical scales of parkinsonismus and psychomotor deficits in 74 patients with a diagnosis of schizophrenia residual type (according to DSM‐IV). Application of special neurorehabilitation method VILAN (V & N Ilankovic, 1997) for improvement of motor disturbances and deficits.
ResultsWe found serious psychomotor disturbances (motor deficiency) in all patients. Dominant disturbances were: abnormality of tonus (100%), posture and postural reflexes (100%), voluntary movements (95%), speech production (95%) and involuntary movements (70%). After application of a special neurorehabilitation program VILAN (in 8 weeks), the results were: reduction of dyspraxio for 86%, disorders of simultan movements for 64%, depressive retardation for 48%, parkinsonism for 44%, abnormal movements for 24% and tardive dyskinesia for 18%.
Conclusions(1) All patients in our clinical study with chronic psychotic states (schizophrenia residual type) have signs of parkinsonismus and other psychomotor deficits. (2) After application of the neurorehabilitation program VILAN, the improvement in parkinsonismus and other motor disturbances was very good. (3) Positive results of specific rehabilitation significantly improve the quality of life of chronic psychotic patients. (4) We conclude that the parkinsonismus, movement disorders and psychomotor deficits are not possible to treat with drugs alone. (5) What is needed is the introduction of functional diagnostic and special psychomotoric rehabilitation in the integrative treatment of chronic psychotic patients. (6) The authors suggest adding movement disorders and psychomotor deficits to the diagnostic criteria of schizophrenia residual type and other chronic psychotic states.