Biomedical subjects

Alan J Thompson

Publications and source records attributed to Alan J Thompson.

At least 19 recordsLinked to original sources

PubMed2007

Two-dimensional population map of cortical connections in the human internal capsule.

PURPOSE: To exploit diffusion imaging tractography to produce a two-dimensional (xy) probabilistic population map of the cortical connections within the human internal capsule (IC). MATERIALS AND METHODS: Diffusion tensor imaging (DTI) was carried out on 11 healthy volunteers. We parceled an axial section of the IC according to its connections to the prefrontal, premotor, primary motor, primary somatosensory, posterior parietal, and occipital cortices using our locally developed probabilistic algorithm. RESULTS: A consistent topographical organization was generated that was consistent with our anatomical knowledge of the IC. In addition, our study shows that in humans the anterior half of the IC is occupied by the prefrontal cortex. CONCLUSION: This map may be of clinical use for correlating neurological deficit with hemispheric lesions, particularly those that affect sensorimotor function.

Adult↗

PubMed2007

Evidence-based guidelines for using the Short Form 36 in cervical dystonia.

We aimed to provide evidence-based guidelines for using the Short Form 36 (SF-36) as an outcome measure in cervical dystonia (CD). To do this, we tested the hypothesized relationships between items, scales, and summary measures of the SF-36 using psychometric analyses in data from a postal survey of 235 people with CD. Although the majority of subscales performed adequately, the Role Physical and Role Emotional subscales had substantial floor and/or ceiling effects. Evidence did not support computing SF-36 Physical and Mental Component Summary scores. We propose guidelines that include the recommendation that these subscale and summary scores should be reported with caution.

Aged↗

PubMed2006

Localization of grey matter atrophy in early RRMS : A longitudinal study.

Previous MR studies have established that grey matter (GM) atrophy occurs in multiple sclerosis (MS) from clinical onset. However, it is uncertain whether early GM atrophy is global or has certain local predilections: using Voxel-Based Morphometry this study aimed to address this question.Twenty-one patients with early RRMS (mean age 36 years, mean disease duration from symptom onset 25.8 months) and 10 healthy control subjects (mean age 37 years) were studied. T(1)-weighted three-dimensional MRI images were acquired at baseline and two year follow-up, and analysed with statistical parametric mapping software (SPM2). Two-sample t-tests (p < 0.05 corrected for multiple comparisons at cluster level) were used to compare GM maps from all patients and controls on a voxel-by-voxel basis. At baseline, no GM region appears significantly atrophic in MS subjects compared with controls. However, during the follow-up period significantly greater atrophy occurred in both thalami and the right lateral prefrontal cortex of MS patients when compared with controls. By year two, cross-sectional group comparison revealed GM atrophy in the thalami of MS patients relative to controls. The rate of thalamic atrophy in MS subjects was correlated with changes in EDSS during the follow-up period. This study suggests that early in the clinical course of RRMS, the thalamic atrophy is more consistently apparent than regional cortical atrophy.

Adult↗

PubMed2006

Selective magnetization transfer ratio decrease in the visual cortex following optic neuritis.

Patients with clinically isolated syndromes suggestive of multiple sclerosis have evidence for abnormality in normal appearing grey matter detected using the magnetization transfer ratio (MTR), a quantitative MRI measure. One potential mechanism for the decreased grey matter MTR (GM MTR) observed is trans-synaptic morphological abnormality secondary to demyelinating lesions that are in an anatomically linked pathway but remote location. We investigated this potential association by studying the location of abnormalities using voxel-based analysis of GM MTR maps in a group of 80 patients studied within 6 months of presenting with isolated optic neuritis and compared the findings with those seen in 50 age- and sex-matched healthy controls. Occipital cortex and whole brain analysis comparing all optic neuritis patients and controls revealed a selective decrease of MTR bilaterally in the visual cortex in patients [Brodmann area (BA) 17]. Whole brain analysis of patients fulfilling the McDonald criteria for multiple sclerosis (n = 20) showed a lower MTR compared to controls bilaterally in the visual cortex (BA 17/18), left hippocampus, bilateral superior temporal gyrus, bilateral lenticular nuclei and the right cerebellum. There was no significant difference in the percentage of grey matter between patients and controls in the regions of abnormal MTR detected in the visual cortex. The intrinsic MTR decrease seen in patients suggests that there are structural changes in the visual cortex following an attack of optic neuritis. Potential mechanisms for this include trans-synaptic neuronal degeneration and cortical synaptic morphological changes; such abnormalities may also contribute to MTR abnormalities observed in the normal appearing grey matter in multiple sclerosis.

Adult↗

PubMed2006

Optic nerve atrophy and retinal nerve fibre layer thinning following optic neuritis: evidence that axonal loss is a substrate of MRI-detected atrophy.

Magnetic resonance imaging (MRI) measures of brain atrophy are often considered to be a marker of axonal loss in multiple sclerosis (MS) but evidence is limited. Optic neuritis is a common manifestation of MS and results in optic nerve atrophy. Retinal nerve fibre layer (RNFL) imaging is a non-invasive way of detecting axonal loss following optic neuritis. We hypothesise that if the optic nerve atrophy that develops following optic neuritis is contributed to by axonal loss, it will correlate with thinning of the RNFL. Twenty-five patients were studied at least 1 year after a single unilateral attack of optic neuritis without recurrence, with a selection bias towards incomplete recovery. They had MR quantification of optic nerve cross-sectional area and optic nerve lesion length, as well as optical coherence tomography (OCT) measurement of mean RNFL thickness and macular volume, quantitative visual testing, and visual evoked potentials (VEPs). Fifteen controls were also studied. Significant optic nerve atrophy (mean decrease 30% versus controls), RNFL thinning (mean decrease 33% versus controls), and macular volume loss occurred in patients' affected eyes when compared with patients' unaffected eyes and healthy controls. The optic nerve atrophy was correlated with the RNFL thinning, macular volume loss, visual acuity, visual field mean deviation, and whole field VEP amplitude but not latency. These findings suggest that axonal loss contributes to optic nerve atrophy following a single attack of optic neuritis. By inference, axonal loss due to other post-inflammatory brain lesions is likely to contribute to the global MRI measure of brain atrophy in multiple sclerosis.

Adult↗

PubMed2006

Motor system activation after subcortical stroke depends on corticospinal system integrity.

Movement-related brain activation patterns after subcortical stroke are characterized by relative overactivations in cortical motor areas compared with controls. In patients able to perform a motor task, overactivations are greater in those with more motor impairment. We hypothesized that recruitment of motor regions would shift from primary to secondary motor networks in response to impaired functional integrity of the corticospinal system (CSS). We measured the magnitude of brain activation using functional MRI during a motor task in eight chronic subcortical stroke patients. CSS functional integrity was assessed using transcranial magnetic stimulation to obtain stimulus/response curves for the affected first dorsal interosseus muscle, with a shallower gradient representing increasing disruption of CSS functional integrity. A negative correlation between the gradient of stimulus/response curve and magnitude of task-related brain activation was found in several motor-related regions, including ipsilesional posterior primary motor cortex [Brodmann area (BA) 4p], contralesional anterior primary motor cortex (BA 4a), bilateral premotor cortex, supplementary motor area, intraparietal sulcus, dorsolateral prefrontal cortex and contralesional superior cingulate sulcus. There were no significant positive correlations in any brain region. These results suggest that impaired functional integrity of the CSS is associated with recruitment of secondary motor networks in both hemispheres in an attempt to generate motor output to spinal cord motoneurons. Secondary motor regions are less efficient at generating motor output so this reorganization can only be considered partially successful in reducing motor impairment after stroke.

Adult↗

PubMed2006

Regional gray matter atrophy in early primary progressive multiple sclerosis: a voxel-based morphometry study.

BACKGROUND: Gray matter (GM) atrophy has been reported in multiple sclerosis (MS). However, little is known about its regional distribution. OBJECTIVE: To investigate the regional distribution of GM atrophy in clinically early primary progressive MS (PPMS). DESIGN AND PATIENTS: Thirty-one patients with PPMS within 5 years of symptom onset (mean age, 43.2 years; median Expanded Disability Status Scale score, 4.5) and 15 healthy control subjects (mean age, 43.7 years) were studied. All subjects underwent a 3-dimensional inversion-recovery fast spoiled gradient-recalled echo sequence that was repeated after 1 year in patients only. Magnetic resonance images underwent an optimized voxel-based morphometric analysis that segments magnetic resonance data volumes in a normalized space and quantifies tissue atrophy on a voxel-by-voxel basis. A lesion mask was created for each patient and used in normalization and segmentation steps to minimize bias from lesions. A multisubject design was used in the cross-sectional study to compare patients with PPMS and controls. A 1-way analysis of variance (within-subjects) design was used in the longitudinal study. RESULTS: At baseline, patients with PPMS displayed bilateral thalamic atrophy compared with controls. In addition, a significant association between lesion load and decreased GM volume was found for the thalami. Loss of GM in the putamen, caudate, thalami, and cortical and infratentorial areas was observed in patients after 1 year of follow-up. CONCLUSIONS: Atrophy is most obvious in deep GM in clinically early PPMS. This may reflect increased sensitivity of these regions to neurodegeneration. Cortical and infratentorial atrophy developed as the disease evolved.

Adult↗

PubMed2006

Upper cervical cord area in early relapsing-remitting multiple sclerosis: cross-sectional study of factors influencing cord size.

PURPOSE: To determine whether the upper cervical cord area (UCCA) is influenced by disease effect in early relapsing-remitting multiple sclerosis (MS), using statistical modeling to account for potential covariates. MATERIALS AND METHODS: A cohort of 39 patients were studied cross-sectionally within three years of first symptom onset (median disease duration = 1.6 years) and compared with 26 healthy controls. The UCCA was measured from axial reconstructions of three-dimensional T1-weighted scans with automated detection of the edge of the cord. Statistical analysis adjusted for factors such as total intracranial volume (TICV) and gender. Clinical correlations, in particular those thought likely to be related to cord pathology, were also investigated. RESULTS: No significant disease effect was noted on UCCA (P = 0.685), although there was borderline evidence of a lower UCCA in patients with symptoms of bowel or bladder disturbance (P = 0.043). A strong association was noted between UCCA and TICV (r = 0.558; P < or = 0.001), and there was a trend for females to have a smaller UCCA (P = 0.062). The latter finding appeared to reflect a gender-related difference in TICV (P < or = 0.001). CONCLUSION: Atrophy of the upper cervical cord is not readily apparent in most patients early in the course of relapsing-remitting MS. In evaluations of disease-related changes in the UCCA in cross-sectional studies, TICV and gender should be considered as potentially confounding covariates.

Adult↗

PubMed2006

Functional anatomy of interhemispheric cortical connections in the human brain.

Interhemsipheric interaction between the human cerebral hemispheres is served by abundant white-matter fibres in the human corpus callosum (CC). Damage to these fibres has notable behavioural and cognitive sequelae that depend on the exact location of the fibre loss. Until now, correlations between fibre loss and neurological disorders have been limited to post-mortem studies. Here we used probabilistic diffusion magnetic resonance imaging tractography to produce a two-dimensional map of the CC in the mid-sagittal plane. We observed an antero-posterior topography of interhemispheric tracts within the CC, consistent with our current neuroanatomical understanding of post-mortem studies in human. Callosal tract to the left and right hemispheres had comparable volume. Gender, a factor that is often reported to affect CC shape and geometry, also had no effect on the volume of the tracts. Our map showed high consistency across individuals. We propose that this map might be useful in the study of the effects of damage to human CC in neurodegenerative and cognitive disorders.

Adult↗

PubMed2006

Longitudinal changes in cerebral response to proprioceptive input in individual patients after stroke: an FMRI study.

OBJECTIVE: Functional magnetic resonance imaging (fMRI) provides an opportunity to study the relationship between cerebral reorganization and functional recovery after stroke. The authors set out to demonstrate the feasibility of using fMRI to investigate mechanisms of recovery in individual patients presenting with severe motor impairment. METHODS: fMRI was performed during passive movement at both affected and unaffected wrists separately in 2 patients with pure motor stroke. Six scanning sessions were performed in each patient over the first 4 months after stroke. Seven control subjects were also studied, 1 of them over 6 sessions. The authors examined for longitudinal changes in cerebral responses to proprioceptive afferent input that correlated with motor recovery. RESULTS: In control subjects, passive movement of either wrist led to relative increases in brain activation in the contralateral sensorimotor cortex and supplementary motor area, the bilateral inferior parietal cortex and secondary somatosensory areas, and the ipsilateral cerebellum. Increases in brain activation correlating with motor recovery were observed in both the ipsilesional primary sensory and primary motor cortex in 1 patient with good motor recovery but not in another patient with poor recovery. No longitudinal changes were seen in the control subject. CONCLUSIONS: These 2 case reports demonstrate that functionally relevant changes in cerebral organization can be identified in individual patients.

Adult↗

PubMed2005

Optic nerve diffusion tensor imaging in optic neuritis.

Diffusion tensor magnetic resonance imaging (DT-MRI) provides in vivo information about the pathology of multiple sclerosis lesions. Increases in mean diffusivity (MD) and reductions in fractional anisotropy (FA) have been found and may represent axonal disruption. The optic nerve is an ideal structure for study by DT-MRI but previous clinical studies did not obtain the full diffusion tensor necessary to calculate MD and FA. In this study, a technique that was specifically developed to achieve full diffusion tensor measurements from the optic nerve (zonal oblique multislice (ZOOM) echoplanar imaging) was applied to 25 patients with a single unilateral episode of optic neuritis at least one year previously, and 15 controls. The intraorbital nerves were segmented on non-diffusion-weighted images and the regions of interest transferred to MD, FA, and eigenvalue maps to obtain quantitative data. Quantitative visual testing and electrophysiology were also performed. In affected nerves, mean MD and mean orthogonal eigenvalue lambda( perpendicular) were elevated, and mean FA reduced compared with clinically unaffected contralateral nerves (P < 0.001) and control nerves (P < 0.001). The mean principal eigenvalue lambda\\ was significantly increased in affected nerves compared to contralateral unaffected nerves (P = 0.04) but not compared to control nerves (P = 0.13). There was no association of clinical measures of visual function in affected eyes with the DT-MRI parameters but there was a significant correlation of the whole field visual evoked potential (VEP) amplitude with MD (r = -0.57, P = 0.006) and lambda( perpendicular) (r = -0.56, P = 0.007). These findings suggest that optic nerve DT-MRI measures provide an indication of the structural integrity of axons.

Adult↗

PubMed2005

Plasma cerebrosterol and magnetic resonance imaging measures in multiple sclerosis.

OBJECTIVES: The concentration in plasma of the brain-specific cholesterol metabolite cerebrosterol has been proposed as a biomarker of neurodegeneration in multiple sclerosis (MS) and other neurological diseases. It is unknown, however, which pathophysiological process in MS best accounts for variations in plasma cerebrosterol. PATIENTS AND METHODS: In this study, we related plasma cerebrosterol concentrations in 46 MS patients - 27 with a relapsing-remitting (RR) disease course and 19 with a primary progressive (PP) course - to three conventional magnetic resonance imaging measures: on T(1)-weighted brain scans, volume of gadolinium-enhanced lesions (a marker of active inflammation) and hypointense lesions (a marker of edema or axonal loss) and on T(2)-weighted scans, volume of hyperintense lesions (a marker of disease extent). RESULTS: By multiple-regression analysis, we uncovered negative correlations between the cerebrosterol-cholesterol ratio in plasma and both age at sampling (beta=-0.35 and p=0.079 in RRMS; beta=-0.76 and p=0.006 in PPMS) and volume of T(2)-weighted lesions (beta=-0.52 and p=0.078 in RRMS; beta=-0.50 and p=0.247 in PPMS). CONCLUSION: We hypothesize that decreases in plasma cerebrosterol may reflect the total spatiotemporal burden of MS-the cumulative effects of its dissemination in space and its duration in time.

Adult↗

PubMed2005

The evolution of prefrontal inputs to the cortico-pontine system: diffusion imaging evidence from Macaque monkeys and humans.

The cortico-ponto-cerebellar system is one of the largest projection systems in the primate brain, but in the human brain the nature of the information processing in this system remains elusive. Determining the areas of the cerebral cortex which contribute projections to this system will allow us to better understand information processing within it. Information from the cerebral cortex is conveyed to the cerebellum by topographically arranged fibres in the cerebral peduncle - an important fibre system in which all cortical outputs spatially converge on their way to the cerebellum via the pontine nuclei. Little is known of their anatomical organization in the human brain. New in vivo diffusion imaging and probabilistic tractography methods now offer a way in which input tracts in the cerebral peduncle can be characterized in detail. Here we use these methods to contrast their organization in humans and macaque monkeys. We confirm the dominant contribution of the cortical motor areas to the macaque monkey cerebral peduncle. However, we also present novel anatomical evidence for a relatively large prefrontal contribution to the human cortico-ponto-cerebellar system in the cerebral peduncle. These findings suggest the selective evolution of prefrontal inputs to the human cortico-ponto-cerebellar system.

Adult↗

PubMed2005

The distribution of magnetic resonance imaging response to interferonbeta-1b in multiple sclerosis.

Whereas the effect of interferons (IFNs) on magnetic resonance imaging (MRI) outcome measures in patients with multiple sclerosis (MS) has been convincingly shown, little work has been done to define the between-patient heterogeneity of treatment response. Our aim was to assess the distribution of the effect of IFNbeta-1b in terms of reduction of active T2 lesions in patients with MS. Using a fixed and a random effects model, we investigated the distribution of active T2 lesions reduction over a three-year follow up in response to treatment with 250 mcg IFNbeta-1b every other day in 695 patients with a complete MRI data-set of the 718 (97 %) enrolled in the European, multicenter, randomised, double-blind, placebo-controlled trial of secondary progressive MS. The two statistical models consistently showed that the between-patient response to IFNbeta-1b, in terms of reduction of active T2 lesions, is highly heterogeneous. Whereas treated patients have a high probability (more than 65%) of showing an active T2 lesion reduction equal to or greater than 60%, there is also a 7% probability for treated patients not to show any reduction of MRI-detected disease activity during the course of the trial or even to have an increase of T2 active lesions. This study might be regarded as a first step toward the definition of markers potentially useful to identify IFNbeta treatment responders and non-responders with regard to T2 lesion activity.

Case-Control Studies↗

PubMed2005

Factors influencing work retention for people with multiple sclerosis: cross-sectional studies using qualitative and quantitative methods.

OBJECTIVE: To identify factors that impact on the ability of patients with multiple sclerosis (MS) to remain in work in order to make recommendations for future clinical management. METHODS: Cross-sectional studies using qualitative (phase one) and quantitative (phase two) methods. In phase one, 62 patients were interviewed and completed an exploratory questionnaire regarding the impact of MS on employment. In phase two, 100 patients attending an MS outpatient clinic completed an impact on work questionnaire, the self-report Barthel index, and the General Health Questionnaire (GHQ-28). RESULTS: In phase one, 17 areas were identified as impacting on MS patients' ability to remain in work, either relating to MS or environment. In phase two, both MS related factors and environmental factors were reported to have a major impact on ability to work. Only 20% of patients had received any advice about work retention. Unemployed patients (N = 64) had greater disability than employed patients on the Barthel index (difference 5.1; p < 0.001), but similar psychological wellbeing on the GHQ-28. CONCLUSION: The issues that prevent people with MS from working tend to be disease-related, as well as work-related. Many patients are isolated, as they are unaware of sources of help. Effective management by healthcare professionals has a potentially important role in helping people with multiple sclerosis to remain employed.

Adolescent↗

PubMed2005

Grey and white matter volume changes in early primary progressive multiple sclerosis: a longitudinal study.

We have recently reported brain atrophy in the early stages of primary progressive multiple sclerosis (PPMS), affecting both grey and white matter (GM and WM). However, to date no clinical or radiological predictors of GM and WM atrophy have been identified. The aim was to investigate short-term changes in GM and WM volumes and to assess the predictive value of demographic, clinical and radiological variables in order to gain a better understanding of the pathological substrate underlying these changes. Thirty-one subjects with PPMS within 5 years of symptom onset were studied at baseline and after 1 year. At baseline, patients underwent neurological examination and were scored on the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite. They had 3D inversion-prepared fast spoiled gradient recalled (FSPGR), dual-echo and triple-dose post-contrast T1-weighted spin echo MRI scans. Proton density and enhancing lesion loads were determined. The 3DFSPGR sequence was repeated after 1 year and brain volume changes were calculated using two techniques, SPM99 (statistical parametric mapping) and SIENA (structural image evaluation, using normalization, of atrophy). Stepwise linear regression models were applied to baseline variables to identify independent predictors of atrophy development. Using SPM99, a decrease in brain parenchymal fraction (-1.03%; P < 0.001) and GM fraction (-1.49%; P < 0.001) was observed. The number of enhancing lesions independently predicted decrease in brain parenchymal fraction (P = 0.019) and decrease in WM fraction (P = 0.002). No independent predictors of GM fraction decrease were found. A mean brain volume change of -0.63% (range -4.27% to +1.18%; P = 0.002) was observed using SIENA, which was independently predicted by EDSS (P = 0.004). Global and GM atrophy can be detected over a 1-year period in early PPMS. The former may be predicted by the degree of inflammation, while the latter seems to be independent of it. SIENA and SPM-based methods appear to provide complementary information.

Adult↗

PubMed2005

The impact of inpatient neurorehabilitation on psychological well-being on discharge and at 3 month follow-up.

INTRODUCTION: Neurological rehabilitation aims to improve quality of life of patients with acute and chronic neurological conditions. Much of the existing research focuses on the impact of rehabilitation on physical functioning, with less emphasis on emotional wellbeing. This study assessed changes in psychological functioning in patients on discharge from rehabilitation and three months after discharge. METHODS: Patients admitted over a six-month period to a neurological rehabilitation unit were recruited prospectively to this study. Psychological functioning was measured by the self-report General Health Questionnaire and the Hospital Anxiety and Depression Scale. In addition, physical functioning was measured by the Barthel index and Functional Independence Measure. RESULTS: Psychological functioning was found to be significantly improved with rehabilitation. However, after three months, patients' scores returned to pre-treatment values. Anxiety was consistently elevated on admission, discharge and follow-up. In contrast, physical functioning improved from admission to discharge and was maintained at follow-up assessment. CONCLUSION: Rehabilitation services need to focus more on psychological functioning after discharge and identify effective strategies to maintain wellbeing.

Activities of Daily Living↗

PubMed2005

Adaptive cortical plasticity in higher visual areas after acute optic neuritis.

The ability to distinguish adaptive cortical reorganization may help to target future therapeutic strategies after neurological insult. We investigated cortical plasticity by prospectively applying visual functional magnetic resonance imaging (fMRI) and optic nerve MRI to 20 patients with acute optic neuritis at baseline, 1, 3, 6, and 12 months. We performed three types of correlation analyses to investigate the relationships between fMRI activity, clinical function, and optic nerve structure. The first analysis directly correlated the fMRI response to clinical function or optic nerve structure and found dynamic relations especially within the first 3 months. The second analysis used a novel technique that modeled the fMRI response and optic nerve structure together with clinical function, to determine the contribution fMRI made to clinical function after accounting for structural factors. Significant effects were found at baseline only, within the right peristriate cortex, and bilaterally in the lateral occipital complexes, which are normally involved in higher order visual processing. The third analysis investigated the relation between the modeled visual recovery rate and fMRI response but found no significant effects. The key findings of this study are from the second analysis and suggest a genuine adaptive role for cortical reorganization within extrastriate visual areas early after optic neuritis.

Adaptation, Physiological↗