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Biomedical subjects

John S Duncan

Publications and source records attributed to John S Duncan.

At least 19 recordsLinked to original sources
PubMed2003

Progressive neocortical damage in epilepsy.

Our objective was to determine the pattern and extent of generalized and focal neocortical atrophy that develops in patients with epilepsy and the factors associated with such changes. As part of a prospective, longitudinal follow-up study of 122 patients with chronic epilepsy, 68 newly diagnosed patients, and 90 controls, serial magnetic resonance imaging scans were obtained 3.5 years apart. Image subtraction was used to identify diffuse and focal neocortical change that was quantified with a regional brain atlas and a fully automated segmentation algorithm. New focal or generalized neocortical volume losses were identified in 54% of patients with chronic epilepsy, 39% of newly diagnosed patients and 24% of controls. Patients with chronic epilepsy were significantly more likely to develop neocortical atrophy than control subjects. The increased risk of cerebral atrophy in epilepsy was not related to a history of documented seizures. Risk factors for neocortical atrophy were age and multiple antiepileptic drug exposure. Focal and generalized neocortical atrophy commonly develops in chronic epilepsy. Neocortical changes seen in a quarter of our control group over 3.5 years were likely to reflect physiological changes. Our results show that ongoing cerebral atrophy may be widespread and remote from the putative epileptic focus, possibly reflecting extensive networks and interconnections between cortical regions.

Adolescent↗
PubMed2003

Functional magnetic resonance imaging of human absence seizures.

We studied a patient with idiopathic generalized epilepsy and frequent absences, using electroencephalogram-correlated functional magnetic resonance imaging. Four prolonged runs of generalized spike-wave discharge occurred during a 35-minute experiment. Time-locked activation was observed bilaterally within the thalami in conjunction with widespread but symmetrical cortical deactivation with a frontal maximum. We demonstrate the reciprocal participation of focal thalamic and widespread cortical networks during human absence seizures and suggest reductions in cortical blood flow, in response to synchronized electroencephalogram activity.

Adult↗
PubMed2003

Three-dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe.

Probabilistic atlases of neuroanatomy are more representative of population anatomy than single brain atlases. They allow anatomical labeling of the results of group studies in stereotaxic space, automated anatomical labeling of individual brain imaging datasets, and the statistical assessment of normal ranges for structure volumes and extents. No such manually constructed atlas is currently available for the frequently studied group of young adults. We studied 20 normal subjects (10 women, median age 31 years) with high-resolution magnetic resonance imaging (MRI) scanning. Images were nonuniformity corrected and reoriented along both the anterior-posterior commissure (AC-PC) line horizontally and the midsagittal plane sagittally. Building on our previous work, we have expanded and refined existing algorithms for the subdivision of MRI datasets into anatomical structures. The resulting algorithm is presented in the Appendix. Forty-nine structures were interactively defined as three-dimensional volumes-of-interest (VOIs). The resulting 20 individual atlases were spatially transformed (normalized) into standard stereotaxic space, using SPM99 software and the MNI/ICBM 152 template. We evaluated volume data for all structures both in native space and after spatial normalization, and used the normalized superimposed atlases to create a maximum probability map in stereotaxic space, which retains quantitative information regarding inter-subject variability. Its potential applications range from the automatic labeling of new scans to the detection of anatomical abnormalities in patients. Further data can be extracted from the atlas for the detailed analysis of individual structures.

Adult↗
PubMed2003

Combined functional MRI and tractography to demonstrate the connectivity of the human primary motor cortex in vivo.

In this study, we combined advanced MR techniques to explore primary motor cortex (M1) connectivity in the human brain. We matched functional and anatomical information using motor functional MRI (fMRI) and white matter tractography inferred from diffusion tensor imaging (DTI). We performed coregistered DTI and motor task fMRI in 8 right-handed healthy subjects and in 1 right-handed patient presenting with a left precentral tumour. We used the fast-marching tractography (FMT) algorithm to define 3D connectivity maps within the whole brain, from seed points selected in the white matter adjacent to the location of the maximum of fMRI activation. Connectivity maps were then anatomically normalised and analysed using statistical parametric mapping software (SPM99) allowing group comparisons (left versus right hemisphere in control subjects and patient versus control subjects). The results demonstrated, in all control subjects, strong connections from M1 to the pyramidal tracts, premotor areas, parietal cortices, thalamus, and cerebellum. M1 connectivity was asymmetric, being more extensive in the dominant hemisphere. The patient had differences in M1 connectivity from the control group. Thus, fMRI-correlated DTI-FMT is a promising tool to study the structural basis of functional networks in the human brain in vivo.

Adult↗
PubMed2003

Non-epileptic seizures: patients' understanding and reaction to the diagnosis and impact on outcome.

RATIONALE: The study aim was to assess patients' understanding of and reaction to a diagnosis of non-epileptic attack disorder and to explore whether these factors contribute to outcome. METHOD: Eighty-four patients diagnosed with non-epileptic attack disorder participated in the study. Participants answered questions about their seizures and understanding and reaction to the diagnosis. Data were collected by semi-structured telephone interview. Questionnaires were sent to the patients' general practitioners (GPs) to gather information regarding the patient's seizure status, prescription of anti-epileptic drugs and opinion regarding the diagnosis. RESULTS: At the time of follow-up, a third of participants reported being seizure free. A total of 63% did not have a good understanding of the diagnosis, most were unclear about the precipitating factors and the most common reaction to the diagnosis was confusion. Many reported a negative impact of NES on everyday life. Sixty-five percent reported receiving psychological follow-up but the number of sessions attended was few (median 2). There was evidence that the reaction to the diagnosis contributed to the outcome in particular an angry outcome was associated with a poor prognosis. Ten GPs did not agree with the diagnosis. CONCLUSION: Patients understanding and reactions to a diagnosis of non-epileptic attacks are important factors that should contribute to the development of more tailored treatment approaches.

Activities of Daily Living↗
PubMed2003

A proton magnetic resonance spectroscopy study of metabolites in the occipital lobes in epilepsy.

PURPOSE: gamma-Amino butyric acid (GABA) and glutamate, respectively the principal inhibitory and excitatory neurochemicals in the brain, are visible to proton magnetic resonance spectroscopy (MRS). We report a study of GABA+ (GABA plus homocarnosine) and GLX (glutamate plus glutamine) concentrations in the occipital lobes in patients with idiopathic generalised epilepsy (IGE) and in patients with occipital lobe epilepsy (OLE). METHODS: Fifteen patients with IGE, 15 patients with OLE, and 15 healthy volunteers were studied. A single voxel was prescribed in the occipital lobes for each subject. PRESS localised short-echo-time MRS was performed to measure GLX by using LCModel. A double quantum GABA filter was used to measure GABA+. Segmented T1-weighted images gave the tissue composition of the prescribed voxel. RESULTS: Grey-matter proportion, GLX, and GABA+ were all elevated in IGE. However, analysis using grey-matter proportion as a covariable showed no significant group differences. No correlation was observed between GABA+ concentration and either seizure frequency or time since last seizure. CONCLUSIONS: GLX and GABA+ were elevated in IGE. Elevated grey-matter content in the IGE group despite normal MRI appearance can be expected to account for some or all of this observed elevation of GLX and GABA+. GABA+ concentration did not correlate with seizure control or duration since most recent seizure.

Adolescent↗
PubMed2003

Grey and white matter flumazenil binding in neocortical epilepsy with normal MRI. A PET study of 44 patients.

In 20-30% of potential surgical candidates with refractory focal epilepsy, standard MRI does not identify the cause. gamma-Aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the brain. [(11)C]Flumazenil (FMZ) PET images most subtypes of GABA(A) receptors, present on most neurons. We investigated [(11)C]FMZ binding in grey and white matter in 16 normal controls and in 44 patients with refractory neocortical focal epilepsy and normal optimal MRI. Fourteen patients had unilateral frontal lobe epilepsy, five occipital lobe epilepsy (OLE), six parietal lobe epilepsy (PLE) and 19 neocortical epilepsy that was not clearly lobar. Parametric images of FMZ volume of distribution (FMZ-V(d)) were computed. Statistical parametric mapping (SPM99) with explicit masking, including the white matter, was used to analyse individual patients and groups. Thirty-three of the 44 patients showed focal abnormal FMZ-V(d); increases in 16, decreases in eight, and both increases and decreases in nine. In seven patients, the increases in FMZ binding were periventricular, in locations normally seen in periventricular nodular heterotopia on MRI. There were frontal and parietal increases in FMZ binding in grey and white matter in the PLE group and decreases in the cingulate gyrus in the OLE group. FMZ binding increases, particularly periventricular increases, were a prominent feature of MRI-negative focal epilepsies and may represent neuronal migration disturbances.

Adolescent↗
PubMed2002

Seizure-induced neuronal injury: human data.

Evidence that recurrent epileptic seizures may cause neuronal injury in some patients has been inferred from clinical observation, neuropsychological assessments, and neuroimaging studies. Cross-sectional investigations have yielded conflicting results and it is not possible to draw conclusions regarding causation, rather than merely association, from such designs. However, there is also evidence from in vivo biochemical studies that seizures may cause neuron injury. The heterogeneity of the epilepsies, epileptic seizures, co-morbidities, treatment regimens, and individual patient susceptibility all complicate the picture and inhibit the drawing of conclusions that are uniformly applicable. Longitudinal neuroimaging studies have the potential to objectively identify structural changes in the brain that are markers of neuronal injury. Such studies are a major undertaking, requiring age-matched control groups and consistent image acquisition and analysis techniques. One needs to analyze not only changes in group means but also the number of patients who show significant changes in imaging parameters that exceed the limits of test-retest reliability and changes in age-matched controls. Quantitative analysis of MRI T(1)-weighted volumetric datasets can reliably identify changes in cerebral and hippocampal volumes of 1-3% in individual subjects. The sensitivity of such quantitative analysis of structural data to identify functionally significant changes is not yet certain. Functional imaging techniques such as MR spectroscopy, PET, and SPECT may be more sensitive for detecting cerebral abnormalities, but their test-retest reliability is inferior. Other MRI tools, such as diffusion tensor imaging, may be useful for evaluating secondary cerebral damage after seizures, both acutely and chronically. Present evidence suggests that, to detect significant treatment effects, longitudinal studies of putative neuroprotective agents, using neuroimaging methods as a surrogate end point, would require at least a 3-year observation period, include large numbers of patients, and provide stratification for important clinical variables.

Brain Injuries↗
PubMed2002

Diffusion tensor imaging in refractory epilepsy.

Diffusion tensor imaging is an imaging method that is sensitive to the molecular movement of water, which indicates cellular integrity and pathology. A patient with refractory epilepsy and normal conventional MRI was examined with diffusion tensor imaging. An area of abnormal diffusion in the right frontal lobe was identified and surgically resected. The patient had a good clinical outcome. Histopathological examination of the resected tissue showed gliosis. Our findings may affect the investigation of similar patients, and provide histopathological confirmation of diffusion abnormalities.

Adult↗
PubMed2002

Partial epilepsy with pericentral spikes: a new familial epilepsy syndrome with evidence for linkage to chromosome 4p15.

The genetic analysis of simple Mendelian epilepsies remains a key strategy in advancing our understanding of epilepsy. In this article, we describe a new family epilepsy syndrome, partial epilepsy with pericentral spikes, which we map to chromosome 4p15. We distinguish it clinically, electrophysiologically, and genetically from previously described Mendelian epilepsies. The family described is a large Brazilian kindred of Portuguese extraction in which affected family members manifest a variety of seizure types, including hemiclonic, hemitonic, generalized tonic-clonic, simple partial (stereotyped episodes of epigastric pain), and complex partial seizures consistent with temporal lobe epilepsy. The syndrome is benign, either requiring no treatment or responding to a single antiepileptic medication. Seizure onset is in the first or second decades of life, with seizures in individuals up to the age of 71 years and documented encephalogram changes up to the age of 30 years. A key feature of partial epilepsy with pericentral spikes is a characteristic encephalogram abnormality of spikes or sharp waves in the pericentral region (centroparietal, centrofrontal, or centrotemporal). This distinctive encephalogram abnormality of pericentral spikes unites these several seizure types into a discrete family epilepsy syndrome. As with other familial epilepsies, the inherited nature of this new syndrome may be overlooked because of the variability in penetrance and seizure types among affected family members.

Adolescent↗
PubMed2002

Exploring white matter tracts in band heterotopia using diffusion tractography.

Band heterotopia is a malformation of cortical development characterized by bands of gray matter in the white matter parallel to the surface of the neocortex. Histopathological studies have suggested that small white matter tracts pass through the heterotopia, and functional magnetic resonance imaging studies have shown activation in the malformation. We used diffusion tractography to explore the anatomical connectivity of band heterotopia and, in particular, whether in vivo white matter tracts traverse the heterotopic gray matter. Five patients with band heterotopia and five control subjects were scanned with whole brain diffusion tensor imaging. Anisotropy maps were calculated. Using fast marching tractography, we produced maps of connectivity and tract traces from two seed points, in the splenium of the corpus callosum and the right parietal lobe. Eigenvectors were found to pass through the band heterotopia in an aligned fashion. Patterns for maps of connectivity were similar in patients and control subjects. Areas of high connectivity were found in the band heterotopia and in cortical areas on the far side of the malformation from the seed point. The tracts hence appeared to traverse or end within the band heterotopia. The results are in agreement with previous histopathological studies and indicate the structural basis of the functional connectivity and absence of focal deficits in these patients.

Adult↗
PubMed2002

The structural consequences of newly diagnosed seizures.

Intractable epilepsy may be associated with widespread structural cerebral damage. We determined whether structural damage occurs to the hippocampus, cerebellum and neocortex in the first few years following a diagnosis of seizures. Sixty-eight patients over the age of 14 years with newly diagnosed seizures and 90 matched controls underwent serial magnetic resonance imaging (MRI) brain scans 3.5 years apart. Using quantitative analysis of serial scans, we determined changes in hippocampal volume, hippocampal T2 relaxometry and total and regional brain volumes. Thirty-four (50%) patients had recurrent unprovoked seizures between baseline and follow-up scans. One patient with pre-existing hippocampal sclerosis (HS) did not develop progressive hippocampal damage. Group analyses found no difference in change in cerebral measures between patients and controls or between patients with and without recurrent seizures. Significant quantitative changes in individuals were largely attributable to pre-existing cerebral lesions or alcohol abuse. Subtle changes detected in individuals over 3.5 years but were not related to a history of overt seizures. Our results show patients with newly diagnosed seizures are not generally at increased risk of seizure-induced structural cerebral damage as detected with MRI. Cerebral damage may occur before the onset of seizures or develop insidiously over a more prolonged period.

Adolescent↗
PubMed2002

MRI studies. Do seizures damage the brain?

Methods to assess the development of cerebral damage need to be quantitative, reliable, reproducible and safe. They must be acceptable to patients and to a healthy control group, for repeated use and the acquisition and analytical methods must be stable over years. Longitudinal studies are necessary to determine whether secondary cerebral damage occurs as a consequence to the epilepsies. The principal aim of longitudinal studies is to detect physical evidence of brain damage when it occurs. Patient groups will be heterogeneous in this regard and analysis will need to be not only of changes in group means, but also of the number of patients who show significant changes in imaging parameters, that exceed the limits of test-retest reliability. MRI is attractive as a tool to evaluate the presence and development of cerebral damage in patients with epilepsy. MRI is readily available and non-invasive, making it acceptable to patients and controls. MRI volumetry is reliable and reproducible, but the sensitivity of the method to detect subtle abnormalities has not yet been established. Longitudinal studies are ongoing in patients with newly diagnosed and chronic epilepsy, with an inter-scan interval of 3.5 years, using complementary voxel-based and region-based methods that can detect changes in hippocampal and cerebellar volumes of 3% and neocortical volume changes of 1.6%. MR spectroscopy may be more sensitive for detecting abnormalities, but the test-retest reliability is less good. Other MRI tools, such as diffusion tensor imaging, may be useful methods for evaluating secondary cerebral damage acutely and chronically.

Brain↗
PubMed2002

Neuroimaging methods to evaluate the etiology and consequences of epilepsy.

Magnetic resonance imaging (MRI) is widely available and is generally the imaging method of first choice for identifying the structural basis of seizure disorders, having both sensitivity and specificity. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) scans may be more sensitive in some patients when MRI is unremarkable, but do not confer specificity of etiological diagnosis. Methods to assess the consequences of epilepsy on the brain need to be quantitative, reliable, reproducible and safe. They must be acceptable to patients and to a healthy control group for repeated use, and the acquisition and analytical methods must be stable over years. Longitudinal studies are necessary to determine whether secondary cerebral damage occurs as a consequence to the epilepsies. Patient groups will be heterogeneous in this regard and analysis will need to be not only of changes in group means, but also of the number of patients who show significant changes in imaging parameters, that exceed the limits of test-retest reliability and of changes in age-matched controls. MRI is an attractive tool to evaluate the presence and development of cerebral damage in patients with epilepsy as it is readily available, non-invasive, and acceptable to patients and controls. MRI volumetry is reliable and reproducible, but the sensitivity of the method to detect subtle abnormalities has not yet been established. Preliminary analysis of longitudinal studies of patients with newly diagnosed and chronic active epilepsy suggests that 10% of newly diagnosed patients and 25% of those with chronic active epilepsy develop significant cerebral, hippocampal or cerebellar atrophy over 3.5 years. MR spectroscopy may be more sensitive for detecting abnormalities, but the test-retest reliability is less good. Other MRI tools such as diffusion tensor imaging (DTI) may be useful methods for evaluating secondary cerebral damage acutely and chronically.

Animals↗
PubMed2002

The epilepsy nurse specialist at a tertiary care hospital-improving the interface between primary and tertiary care.

Recent literature suggests that access to an epilepsy nurse specialist (ENS) may help improve patients understanding and management of their condition and in doing so may decrease morbidity and mortality. This paper describes the role of the ENS at a large tertiary referral epilepsy centre, the National Hospital for Neurology and Neurosurgery (NHNN) in supporting patients with refractory epilepsy in the hospital and community. Approximately 300 patients were referred to the ENS in the first 6 months of the service. A questionnaire was posted to 193 patients, 69% responded. Most patients had multiple seizures each month, took polytherapy, underwent frequent antiepileptic drug (AED) dose changes and often experienced drug side effects. Sixty percent of patients contacted the ENS for urgent medical advice. Important aspects of the service were access by telephone to medication advice, information, support and adequate time to discuss issues. The ENS improved continuity of, and accessibility to, care for patients, has become a key member of the multidisciplinary epilepsy team and has freed up scarce medical time.

Adult↗