Papers by Roderick Duncan
Human molecular genetics, Jan 4, 2015
Numerous diverse biological pathways are dysregulated in the epileptic focus. Which of these path... more Numerous diverse biological pathways are dysregulated in the epileptic focus. Which of these pathways are most critical in producing the biological abnormalities that lead to epilepsy? Answering this question is key to identifying the primary causes of epilepsy and for discovering new therapeutic strategies with greater efficacy than currently available antiepileptics (AEDs). We have performed the largest genome-wide transcriptomic analysis to date comparing epileptic with normal human hippocampi. We have identified 118 differentially expressed and, for the first time, differentially connected pathways in the epileptic focus. Using network mapping techniques, we have shown that these dysregulated pathways, though seemingly disparate, form a coherent interconnected central network. Using closeness centrality analysis, we have identified that the most influential hub pathways in this network are signalling through G protein-coupled receptors, in particular opioid receptors, and their ...
Eur J Nucl Med Mol Imaging, 2003
Vagus nerve stimulation (VNS) has gained recognition as a treatment for refractory epilepsies whe... more Vagus nerve stimulation (VNS) has gained recognition as a treatment for refractory epilepsies where surgical treatment is not possible. While it appears that this treatment is effective in some patients, the mechanism of action is not clearly understood. The purpose of this study was to clarify findings of other positron emission tomography and single-photon emission tomography (SPET) investigations by measuring the acute effect of VNS on patients who have normal cerebral anatomy on magnetic resonance imaging and who have not previously been exposed to VNS. We investigated six subjects (two males and four females, mean age 29.5 years, range 21-39 years) with intractable epilepsy. One patient had primary generalised epilepsy causing generalised tonic-clonic seizures; the remaining five patients had localisation-related epilepsy causing complex partial seizures. SPET imaging was performed using 250 MBq of (99m)Tc-HMPAO and a four-scan paradigm - two with and two without stimulation. The stimulation began at VNS current levels of 0.25 mA and was increased according to the limit of patients' tolerance, usually defined by coughing or discomfort. The stimulating waveform was of continuous square wave pulses of 500 micro s duration at 30 Hz. Image analysis was by SPM99. Reduced perfusion during stimulation was observed in the ipsilateral brain stem, cingulate, amygdala and hippocampus and contralateral thalamus and cingulate. The study provides further evidence of the involvement of the limbic system in the action of vagal nerve stimulation.
Journal of Nuclear Medicine, May 1, 1999
The distribution of sodium amytal and its effect on regional cerebral perfusion during the intrac... more The distribution of sodium amytal and its effect on regional cerebral perfusion during the intracarotid amytal (Wada) test were investigated using high-resolution hexamethyl propyleneamine oxime (HMPAO) SPECT coregistered with the pa tient's MRI dataset. Methods: Twenty patients underwent SPECT after intravenous HMPAO injection, and 5 patients had both intravenous and intracarotid injections in a double injectionacquisition protocol. Results: All patients had hypoperfusion in the territories of the anterior and middle cerebral arteries. Basal ganglia perfusion was preserved in 20 of 25 patients. Hypoperfu sion of the entire mesial temporal cortex was seen in 9 of 25 patients. Partial hypoperfusion of the whole mesial cortex or hypoperfusion of part of the mesial cortex was seen in 14 of 25 patients. In 2 of 25 patients, mesial temporal perfusion was unaffected. In 5 patients, the double acquisition showed a distribution of HMPAO delivery matching that of hypoperfusion, except for the following: (a) HMPAO was delivered to the basal ganglia and insula, where there was no hypoperfusion; (b) HMPAO was not delivered to the contralateral cerebellum, which did show hypoperfusion; and (c) in 1 patient, perfusion of the mesial temporal cortex was preserved despite intracarotid deliv ery of HMPAO. Conclusion: Some degree of hypoperfusion of medial temporal structures occurs in the great majority of patients during the Wada test. Partial inactivation of memory structures is therefore a credible mechanism of action of the test. The double acquisition protocol provided no evidence that mesial temporal structures are inactivated remotely by diaschisis. Perfu sion in the basal ganglia and insular cortex is not affected by amytal.
Journal of Neurology Neurosurgery and Psychiatry, 1991
Patient Education and Counseling, 2011
This qualitative study analyses patients' conversational behaviours to explore whether there are ... more This qualitative study analyses patients' conversational behaviours to explore whether there are interactional factors that could explain why doctors find clinical encounters in which the diagnosis of functional symptoms (physical symptoms with presumed emotional causes) is explained and psychological treatment offered particularly challenging. Methods: Twenty out-patient consultations between neurologists and patients with functional symptoms were recorded and analysed using Conversation Analysis. Patients' communication behaviour was characterised by pervasive interactional resistance. Instances of resistance were identified and counted. Results: Interactional resistance was especially evident when the aetiology of symptoms and treatment recommendations were discussed. Resistance was expressed overtly (through disagreements, challenges, rejections) or more passively (through moves such as lack of engagement with the interaction, silences or the use of minimal responses). This study provides objective evidence that doctors face interactional challenges when they try to explain that symptoms are medically unexplained and suggest psychological treatment. Practice implications: Doctors may try to avoid provoking patients' overt resistance because they perceive it as unpleasant. However, the display of overt resistance enables them to deal explicitly with the grounds on which patients reject their explanations and recommendations, and to address patients' particular concerns.
Journal of neurology, neurosurgery, and psychiatry, 2015
Somatic symptoms unexplained by disease are common in all medical settings. The process of identi... more Somatic symptoms unexplained by disease are common in all medical settings. The process of identifying such patients requires a clinical assessment often supported by clinical tests. Such assessments are time-consuming and expensive. Consequently the observation that such patients tend to report a greater number of symptom has led to the use of self-rated somatic symptom counts as a simpler and cheaper diagnostic aid and proxy measure for epidemiological surveys. However, despite their increasing popularity there is little evidence to support their validity. We tested the score on a commonly used self-rated symptom questionnaire- the Patient Health Questionnaire (PHQ 15) (plus enhanced iterations including an additional 10 items on specific neurological symptoms and an additional 5 items on mental state) for diagnostic sensitivity and specificity against a medical assessment (with 18 months follow-up) in a prospective cohort study of 3781 newly attending patients at neurology clinic...
Neuropsychologia, 2005
Electrical stimulation of the temporal cortex in patients with epilepsy sometimes elicits experie... more Electrical stimulation of the temporal cortex in patients with epilepsy sometimes elicits experiential phenomena such as recollection of vivid memories. The neurophysiological substrate of such phenomena is poorly understood. Furthermore, the relation between the site of stimulation and the type of memory elicited has only recently started to be investigated. We investigated these issues in patient FGA who had intracerebral electrodes stereotaxically implanted in the right temporal lobe for investigation of drug-resistant epilepsy. We report the results of electrical stimulations of the perirhinal region. Two stimulations elicited experiential phenomena consisting of visual memories that belonged to FGA's past, but which were not related to any particular episode. These visual memories consisted of objects or of details of objects. These two stimulations were contrasted with other stimulations in the same subhippocampal region. Cross-correlation analysis of the depth-EEG signals filtered in frequency sub-bands revealed that experiential phenomena occurred only when the various brain structures involved in the after-discharge were synchronized in the theta range. These structures included the perirhinal region, the hippocampus, other limbic structures as well as a primary visual area. Our results suggest that recollection of vivid memory after electric stimulation of the cortex may rely on wide networks of brain areas that transiently synchronize. These results also highlight the role of the perirhinal region in human memory. Experiential phenomena are rarely obtained after brain stimulation. Replication of these results is thus required due to the small number of observations reported.
Seizure, 2003
Clinical practice with people with intellectual disability relies heavily upon caregiver report. ... more Clinical practice with people with intellectual disability relies heavily upon caregiver report. Crucially, the carer's perspective may depend upon his or her relationship to the patient. We investigated similarities and differences within and between family and paid carers in their reports on the Glasgow Epilepsy Outcome Scale (GEOS), an instrument that quantifies concerns about epilepsy in this population [Epilepsia 42 (2001) 1043]. GEOS forms were available on 186 patients (108 males; mean age 39 years) across 384 primary respondents (141 staff, 83 family, 160 clinicians) and independently completed secondary respondents (67 staff, 36 family). Data were analysed to consider levels of concern as rated bv staff carers, family members and clinicians, and also to consider inter-rater agreement on the concerns raised. There were significant differences in the magnitude of concern on each sub-scale [concerns about seizures, treatment, caring and social impact; range of F(2,171)=9.5-64.7; all P<0.0001]. Post hoc testing revealed that family members scored all sub-scales more highly than staff carers or clinicians, and that staff carers scored more highly than clinicians on all but one sub-scale. Inter-rater agreement between family members was considerably higher (range of r=0.69-0.91) than between staff carers (r=0.30-0.47) across the GEOS sub-scales. Association between staff and family ratings was also modest (r< or = 0.39). It is preferable for the same staff member to complete each administration of the GEOS because of inter-staff variability in reporting of concerns. Families provide a consistent, but more extreme, picture and clinicians generally underestimate the concerns of direct caregivers. However, content of concerns varies relatively little across respondents.
Seizure, 1997
99mTC (single photon emission computed tomography) (HMPAO SPECT) was carried out during 16 fronta... more 99mTC (single photon emission computed tomography) (HMPAO SPECT) was carried out during 16 frontal-lobe seizures in 15 patients. Focal changes in regional cerebral blood flow were seen during all seizures. In 9 of 16 seizures SPECT showed hyperperfusion localized to one frontal lobe. In 1 of 16 seizures ictal hypoperfusion was seen in one frontal lobe. In 2 of 16 seizures there was hyperperfusion in both frontal lobes, and in 4 of 16 seizures hyperperfusion involved the frontal lobe or lobes plus other lobes of the brain. These changes were accompanied by hyperperfusion of subcortical structures in 13 seizures. SPECT thus localized to one frontal lobe in 10 of 16 seizures, and localized to the frontal lobes without lateralizing in two further seizures. No seizure showed a pattern of perfusion similar to that reported in mesial-temporal-lobe seizures. We conclude that ictal SPECT may provide useful localizing information in frontal-lobe seizures.
The Lancet, 1987
1. Lancet. 1987 Sep 12;2(8559):625-6. Reversible cerebellar diaschisis in focal epilepsy. Duncan ... more 1. Lancet. 1987 Sep 12;2(8559):625-6. Reversible cerebellar diaschisis in focal epilepsy. Duncan R, Patterson J, Bone I, Wyper DJ. PMID: 2887908 [PubMed - indexed for MEDLINE]. Publication Types: Case Reports; Letter; Research Support, Non-US Gov't. MeSH Terms: ...
Journal of Psychosomatic Research, 2011
Objective: Consultations with patients with functional symptoms can be challenging. This study de... more Objective: Consultations with patients with functional symptoms can be challenging. This study describes some of the interactional and linguistic resources doctors use when they deliver the diagnosis of a functional disorder and recommend psychological treatment to patients presenting with medically unexplained neurological symptoms. Methods: Twenty out-patient consultations between three experienced neurologists and patients with nonepileptic seizures (NES, N = 17) or other functional neurological symptoms (FNS, n = 3) were recorded and analysed using Conversation Analysis (CA). Encounters were split into activity sequences (1: history-taking; 2: discussion of examination and test results; 3: diagnosis; 4: aetiology; 5: treatment recommendations). The doctors' formulation effort (FE) in each activity sequence was graded (1: little, 2: some, 3: marked FE). Results: The doctors' communication behaviour was characterised by FE and accounting activities. FE increased during the course of the encounters and was most marked when doctors discussed the aetiology of symptoms and made psychological treatment recommendations. However, FE was evident even at the beginning of the encounters, and when patients fully aligned with the doctor. Conclusion: This study provides interactional evidence why doctors may experience these consultations as challenging. While FE and accounting activities were sometimes linked to objective interactional problems (patients' resistance), doctors also seemed to engage in these practices for no clear interactional reasons, suggesting a degree of defensiveness or prior concern about the consultation. The extent of FE and accounting activities may display doctors' interactional distress but may also reflect a degree of delicacy when doctors explain the diagnoses of NES or FNS.
Journal of Neurology, Neurosurgery & Psychiatry, 2011
Background In clinical practice, it is sometimes observed that patients in whom psychogenic nonep... more Background In clinical practice, it is sometimes observed that patients in whom psychogenic nonepileptic seizures (PNES) cease, develop another medically unexplained symptom (MUS). Methods In order to determine how many patients develop new MUS post diagnosis and whether patients whose attacks cease are more likely to do so, new MUS were recorded 6e12 months after the diagnosis of PNES in 187 consecutive patients. Results Compared with baseline, the overall proportion of patients with MUS increased slightly, from 70.1% to 76.5%, with 44/187 patients (23.5%) developing new MUS. There were no significant differences between attack free and non-attack free patients. Binary logistic regression analysis showed that predictors of new MUS diverged between attack free and non-attack free patients. Among patients continuing to have attacks, those with previous health related psychological trauma were 18.00 times more likely to develop new MUS (p<0.0005). In patients who became attack free, patients drawing disability benefits were 5.04 times more likely to have new MUS (p¼0.011).
Journal of Neurology, Neurosurgery & Psychiatry, 2012
Functional neurological symptoms (FNS) are commonly encountered but have engendered remarkably li... more Functional neurological symptoms (FNS) are commonly encountered but have engendered remarkably little academic interest. 'UK-Functional Neurological Symptoms (UK-FNS)' was an informal inaugural meeting of UK based clinicians in March 2011 with a variety of research and clinical interests in the field. This narrative review reflects the content of the meeting, and our opinion of key findings in the field since the turn of the millennium.
Journal of Neurology, Neurosurgery & Psychiatry, 2014
Background and objectives There have been few studies of long-term outcome in psychogenic nonepil... more Background and objectives There have been few studies of long-term outcome in psychogenic nonepileptic seizures (PNES), and none of long-term healthcare utilization. Methods We studied attendance with seizures, healthcare use and employment over a 6-month period from the family doctors of 260 consecutive patients with psychogenic non-epileptic seizures (PNES), 5-10 years after diagnosis. Results We obtained clinical data in 188/260 patients (72.3%), of whom 60 (31.9%) had attended primary or secondary care with seizures in the previous 6 months. Predictors of attendance with seizures included a diagnosis of epilepsy+PNES (OR 5.7, p=0.009), work status (OR 3.9, p=0.027) and social security payments (OR 6.3, p=0.003). Latency to diagnosis was not predictive. Emergency admission data were available in 187 patients, of whom 25 (13.4%) had emergency hospital attendances. Prescription data were available for 172 patients, of whom 154 had 'PNES only'. Of these, 17 (11.0%) remained on antiepileptic medication (AED). 68/172 patients (39.5%) were prescribed antidepressant (AD) drugs. We had psychiatric contact data in 185 patients, of whom 49 (26.5%) had accessed psychiatric services in the last 6 months.
European Journal of Nuclear Medicine and Molecular Imaging, 2003
Vagus nerve stimulation (VNS) has gained recognition as a treatment for refractory epilepsies whe... more Vagus nerve stimulation (VNS) has gained recognition as a treatment for refractory epilepsies where surgical treatment is not possible. While it appears that this treatment is effective in some patients, the mechanism of action is not clearly understood. The purpose of this study was to clarify findings of other positron emission tomography and single-photon emission tomography (SPET) investigations by measuring the acute effect of VNS on patients who have normal cerebral anatomy on magnetic resonance imaging and who have not previously been exposed to VNS. We investigated six subjects (two males and four females, mean age 29.5 years, range 21-39 years) with intractable epilepsy. One patient had primary generalised epilepsy causing generalised tonic-clonic seizures; the remaining five patients had localisation-related epilepsy causing complex partial seizures. SPET imaging was performed using 250 MBq of (99m)Tc-HMPAO and a four-scan paradigm - two with and two without stimulation. The stimulation began at VNS current levels of 0.25 mA and was increased according to the limit of patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; tolerance, usually defined by coughing or discomfort. The stimulating waveform was of continuous square wave pulses of 500 micro s duration at 30 Hz. Image analysis was by SPM99. Reduced perfusion during stimulation was observed in the ipsilateral brain stem, cingulate, amygdala and hippocampus and contralateral thalamus and cingulate. The study provides further evidence of the involvement of the limbic system in the action of vagal nerve stimulation.
Epilepsy & Behavior, 2012
Patients with temporal lobe epilepsy (TLE) often present with memory complaints despite performin... more Patients with temporal lobe epilepsy (TLE) often present with memory complaints despite performing within normal limits on standard memory tests. One possible explanation for this phenomenon is accelerated long-term forgetting (ALF). The present study investigated material-specific ALF in patients with unilateral TLE and also examined whether ALF could be demonstrated on a novel, standardized anterograde autobiographical memory (ABM) task. Fourteen patients with TLE and 17 controls were administered verbal, nonverbal and ABM event memory tasks. The participants were tested for immediate recall, recall and recognition at 30-minute delay, and recall and recognition after four weeks. The extent of ALF was calculated based on the percentage decay of memory from the 30-minute delay trial to the four-week delay trial. Patients with left TLE showed significantly greater ALF for verbal material and a trend towards greater forgetting of ABM. Patients with right TLE showed a non-significant trend towards greater ALF for nonverbal material. Patients with unilateral hippocampal abnormalities showed greater ALF compared to patients without hippocampal abnormalities. Patients with seizures that generalize had more global memory deficits and greater ALF. We conclude that patients with unilateral TLE show material-specific ALF, which appears to be more pronounced with an abnormal hippocampus or seizures that secondarily generalize.
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Papers by Roderick Duncan