Biomedical subjects

A J Thompson

Publications and source records attributed to A J Thompson.

At least 73 records · Page 4Linked to original sources

PubMed2003

Magnetic resonance studies of abnormalities in the normal appearing white matter and grey matter in multiple sclerosis.

Magnetic resonance (MR) techniques are of value in following the pathological process of multiple sclerosis in vivo. They are widely applied to monitor the disease natural history and its modification by treatment. However, serial studies of lesion measures have yielded generally disappointing correlations with the development of clinical disability. A potential explanation for this is the presence of abnormalities, beyond the visible lesions, in the normal appearing white matter (NAWM) and grey matter (NAGM). Quantitative structural MR techniques, including measures of magnetisation transfer, diffusion, relaxation times and spectroscopic metabolite concentrations, reveal that there are abnormalities in NAWM and NAGM. These are present from clinical onset and become more pronounced with clinical progression, increasing disability and increasing lesion load. Furthermore, functional MRI (fMRI) studies of motor and visual paradigms has identified a range of responses suggesting that cortical plasticity exists; such modified responses are seen in the earliest stages of disease and in the absence of visible lesions, but are more pronounced with disease progression and increasing lesion load and abnormality in the NAWM. Limited reproducibility and sensitivity to change can pose methodological limitations for MR studies of NAWM and NAGM, especially when follow up intervals are relatively short. Whilst existing quantitative MR measures from normal appearing tissues provide valuable information to understand the natural history and monitor treatment effects in MS, none of them fully or even predominantly accounts for the patient's functional state nor can be relied on as a definitive surrogate measure of treatment effect. Better resolution of the abnormalities is needed especially in grey matter where pathological foci are known to be abundant. Studies correlating structural MR and fMRI parameters with measures of function in well defined anatomical pathways should further elucidate the pathogenic role of abnormality in the normal appearing tissues. In future, new imaging modalities are needed that provide a more specific measure of histopathological and cellular aspects of the disease process in vivo.

Brain↗

PubMed2003

The normal appearing grey matter in primary progressive multiple sclerosis: a magnetisation transfer imaging study.

BACKGROUND: In 10-15 % of patients with multiple sclerosis (MS), the clinical course is characterized by slow progression in disability without relapses (primary progressive (PP) MS). The mechanism of disability in this form of MS is poorly understood. Using magnetization transfer ratio (MTR) imaging, we investigated normal appearing white matter (NAWM) and normal appearing grey matter (NAGM) in PPMS and explored the relationship of MTR measures with disability. METHODS: Thirty patients with PPMS and 30 age matched controls had spin echo based MTR imaging to study lesions and normal appearing tissues. The brain was segmented into NAWM and NAGM using SPM99 with lesions segmented using a semiautomated local thresholding technique. A 75% probability threshold for classification of NAWM and NAGM was used to diminish partial volume effects. From normalized histograms of MTR intensity values, six MTR parameters were measured. Mean lesion MTR and T2 lesion volume were also measured. Disability was assessed using Kurtzke's expanded disability status scale (EDSS). RESULTS: Compared with controls, patients exhibited a significant reduction in mean NAWM (p = 0.001) and NAGM (p = 0.004) MTR. Spearman's rank correlation of EDSS with the six MTR parameters in NAWM and NAGM, mean lesion MTR, and T2 lesion volume, was only significant with mean NAGM MTR (r = -0.41, p = 0.02), the 25th percentile of NAGM MTR intensity (r = -0.37, p = 0.05), and T2 lesion volume (r = 0.39, p = 0.04). Multiple regression analysis of the relationship between EDSS and 4 MR parameters representing each tissue type (mean NAWM MTR, mean NAGM MTR, mean lesion MTR, T2 lesion volume) showed that the association of EDSS with mean NAGM MTR remained significant. CONCLUSIONS: There appear to be significant abnormalities in the NAGM in PP MS. Further investigation of the pathological basis and functional significance of grey matter abnormality in PPMS is warranted.

Adult↗

PubMed2003

From diffusion tractography to quantitative white matter tract measures: a reproducibility study.

The aim of this study is to propose methods for assessing the reproducibility of diffusion tractography algorithms in future clinical studies and to show their application to the tractography algorithm developed in our unit, fast marching tractography (FMT). FMT estimates anatomical connectivity between brain regions using the information provided by diffusion tensor imaging. Three major white-matter pathways were investigated in 11 normal subjects--anterior callosal fibers, optic radiations, and pyramidal tracts. FMT was used to generate maps of connectivity metric, and regions of voxels with highest connectivity metric to an anatomically defined starting point were identified for each tract under investigation. The reproducibilities of tract-"normalized" volume (NV) and fractional anisotropy (FA) measurements were assessed over such regions. The values of tract volumes are consistent with the postmortem data. Coefficients of variation (CVs) for FA and NV ranged from 1.7 to 7.1% and from 2.2 to 18.6%, respectively. CVs were lowest in the anterior callosal fibers (range: 1.7- 7.8%), followed by the optic radiations (range: 1.2-18.6%) and pyramidal tracts (range: 2.6-15.5%), suggesting that fiber organization plays a role in determining the level of FMT reproducibility. In conclusion, these findings underline the importance of assessing the reliability of diffusion tractography before investigating white matter pathology.

Adult↗

PubMed2003

Diffusion tractography based group mapping of major white-matter pathways in the human brain.

Tractography uses diffusion tensor imaging data to trace white matter pathways in vivo within the brain. We have constructed group maps that represent three major white matter tracts-the anterior callosal fibers, optic radiations, and pyramidal tracts-in a group of 21 volunteers. For each individual tract the fast marching tractography (FMT) algorithm was used to generate a VSC (voxel scale connectivity) map in native space. Using SPM99 these maps were transformed into a standard reference frame and three group mapping techniques were investigated: the first averaged the individual VSC maps, the second produced maps that demonstrate intersubject tract variability and degree of overlap, and the third used an SPM analysis to construct a statistical image that represents the group effect. The group maps reconstructed for each tract under investigation conform well to known anatomy and are consistent with data derived from postmortem human brains. Greater intersubject variability is found around the terminal projections of the tracts adjacent to cerebral cortex, whereas the "core" of each tract is characterized by lower variability. No significant differences were found between the left and right side of the pyramidal tracts and optic radiations. The group mapping techniques utilize the VSC maps in different but complementary ways. In the future, group mapping could investigate in vivo white matter differences between normal subjects and patients affected by neurological and psychiatric diseases.

Adult↗

PubMed2003

Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging.

Evidence concerning anatomical connectivities in the human brain is sparse and based largely on limited post-mortem observations. Diffusion tensor imaging has previously been used to define large white-matter tracts in the living human brain, but this technique has had limited success in tracing pathways into gray matter. Here we identified specific connections between human thalamus and cortex using a novel probabilistic tractography algorithm with diffusion imaging data. Classification of thalamic gray matter based on cortical connectivity patterns revealed distinct subregions whose locations correspond to nuclei described previously in histological studies. The connections that we found between thalamus and cortex were similar to those reported for non-human primates and were reproducible between individuals. Our results provide the first quantitative demonstration of reliable inference of anatomical connectivity between human gray matter structures using diffusion data and the first connectivity-based segmentation of gray matter.

Adult↗

PubMed2003

Neural correlates of outcome after stroke: a cross-sectional fMRI study.

Recovery of motor function after stroke may occur over weeks or months and is often attributed to neuronal reorganization. Functional imaging studies investigating patients who have made a good recovery after stroke have suggested that recruitment of other motor-related networks underlies this recovery. However, patients with less complete recovery have rarely been studied, or else the degree of recovery has not been taken into account. We set out to investigate the relationship between the degree of recovery after stroke and the pattern of recruitment of brain regions during a motor task as measured using functional MRI. We recruited 20 patients who were at least 3 months after their first ever stroke, and 26 right-handed age-matched control subjects. None of our patients had infarcts involving the hand region of the primary motor cortex. All subjects were scanned whilst performing an isometric, dynamic visually paced handgrip task. The degree of functional recovery of each patient was assessed using a battery of outcome measures. Single-patient versus control group analysis revealed that patients with poor recovery were more likely to recruit a number of motor-related brain regions over and above those seen in the control group during the motor task, whereas patients with more complete recovery were more likely to have 'normal' task-related brain activation. Across the whole patient group and across stroke subtypes, we were able to demonstrate a negative correlation between outcome and the degree of task-related activation in regions such as the supplementary motor area, cingulate motor areas, premotor cortex, posterior parietal cortex, and cerebellum. This negative correlation was also seen in parts of both contralateral and ipsilateral primary motor cortex. These results further our understanding of the recovery process by demonstrating for the first time a clear relationship between task-related activation of the motor system and outcome after stroke.

Adult↗

PubMed2003

The longitudinal relation between brain lesion load and atrophy in multiple sclerosis: a 14 year follow up study.

BACKGROUND: Studies have suggested that T2 lesion activity is prominent in early relapsing-remitting multiple sclerosis, whereas brain atrophy, while seen early, appears more evident in later progressive disease. The temporal relation between these processes remains unclear. OBJECTIVE: To explore the association between changing brain lesion loads and subsequent tissue atrophy in multiple sclerosis. METHODS: 28 subjects with clinically probable or definite multiple sclerosis (mean age 46.0 years; 17 female and 11 male) were followed for 14 years after first onset of symptoms. T2 lesion loads were estimated soon after symptom onset and at around five, 10, and 14 years later. Disease related atrophy was estimated at the 14 year follow up by comparing brain tissue volumes (proportional to total intracranial volumes) determined in the multiple sclerosis group with data from 29 normal control subjects (mean age 36.7 years; 16 female, 13 male) using multiple linear regression analyses to allow for differences in age and sex distributions. RESULTS: Change in lesion load in the first five years was more closely correlated to disease related brain atrophy at 14 years than later changes in lesion load, although the correlation was only moderate (Spearman correlation = -0.528, p = 0.004). CONCLUSIONS: From this, it appears that early rather than later focal lesion accumulation relates to subsequent brain atrophy, but factors unconnected directly with lesion formation probably also play a significant role in determining such atrophy.

Adult↗

PubMed2003

Spinal cord MRI in clinically isolated optic neuritis.

BACKGROUND/METHODS: One hundred and fifteen patients with clinically isolated optic neuritis underwent magnetic resonance imaging (MRI) of the brain and spinal cord within 3 months of the onset of symptoms. RESULTS: Eighty one (70%) patients had brain lesions and 31 (27%) had cord lesions. Cord lesions were seen in 12% with a normal brain MRI, 21% with between one and eight brain lesions, and 45% with nine or more brain lesions. When the new diagnostic criteria for MS were applied, MRI cord imaging used for evidence of dissemination in time and space allowed a diagnosis of MS in only one additional asymptomatic patient at 1 year, two additional asymptomatic patients at 3 years. CONCLUSIONS: Using existing criteria, spinal cord imaging rarely contributes to the diagnosis in patients with clinically isolated optic neuritis.

Adolescent↗

PubMed2003

Using the SF-36 measure to compare the health impact of multiple sclerosis and Parkinson's disease with normal population health profiles.

OBJECTIVE: To examine the relative impact of two chronic neurological disorders, multiple sclerosis and Parkinson's disease, by comparing patients' scores on the medical outcomes study 36-item short form health survey (SF-36) with the health profile of the United Kingdom population norms. METHODS: 638 people representing the full spectrum of multiple sclerosis and 227 patients with Parkinson's disease were studied. Health status was measured by the SF-36. Scores for the eight health domains were compared after controlling for age, sex, disease duration, mobility, social class, ethnicity, education, marital status, and employment status. RESULTS: People with multiple sclerosis and those with Parkinson's disease had significantly worse health than the general population on all eight domains measured by the SF-36. The relative impact of multiple sclerosis and Parkinson's disease were similar, but multiple sclerosis resulted in poorer scores on physical functioning and better scores in mental health. People with mild multiple sclerosis who walked without an aid also had significantly worse scores in all dimensions than the general UK population. CONCLUSIONS: The results highlight the need for further research into aspects of health measured by the SF-36. Nevertheless, generic measures that are applicable across multiple diseases may fail to address clinically important aspects of the impact of specific disorders.

Adult↗

PubMed2003

Interferon beta in multiple sclerosis: experience in a British specialist multiple sclerosis centre.

BACKGROUND: The efficacy of interferon beta (IFN beta) is well established in relapsing-remitting multiple sclerosis (MS). However, the use of this drug in clinical practice is complex, especially because it is only partially effective, its long term efficacy and side effects are unknown, its efficacy may be abrogated by the development of neutralising antibodies, compliance is variable, and its cost effectiveness is controversial. OBJECTIVES AND METHODS: Analysis of a prospectively followed up series of 101 MS patients treated with IFN beta was undertaken to: (1) monitor the outcome of IFN beta treatment in clinical practice; (2) compare the immunogenicity of the three commercial IFN beta preparations available; (3) assess the proportion of patients fulfilling the current guidelines of the Association of British Neurologists for stopping IFN beta therapy. RESULTS: During a median treatment period of 26 months (range 2-85), the relapse rate decreased by 41%. Although the reduction in the relapse rate was similar for all three commercial products, none of the Avonex treated patients were relapse free, compared with 19% of the Betaferon treated and 27% of the Rebif treated patients (p=0.02). Neutralising antibodies were not detected in Avonex treated patients (0 of 18), compared with 12 of 32 (38%) Betaferon treated and 10 of 23 (44%) Rebif treated patients (p=0.02). Forty of 101 (40%) patients satisfied the current (2001) Association of British Neurologists criteria for stopping IFN beta treatment at some stage during their treatment. CONCLUSION: IFN beta is effective in reducing the relapse rate in patients with relapsing-remitting MS in routine clinical practice. However, after a median treatment duration of 26 months, 40% of initially relapsing-remitting MS patients seem to have ongoing disease activity, presenting as disabling relapses or insidious progression.

Adjuvants, Immunologic↗

PubMed2003

Diffusion tensor imaging detects corticospinal tract involvement at multiple levels in amyotrophic lateral sclerosis.

BACKGROUND: Histopathological studies of amyotrophic lateral sclerosis (ALS) are of end stage disease. Diffusion tensor imaging (DTI) provides the opportunity to investigate indirectly corticospinal tract pathology of ALS in vivo. METHODS: DTI was used to study the water diffusion characteristics of the corticospinal tracts in 21 patients with ALS and 14 normal controls. The authors measured the fractional anisotropy (FA) and mean diffusivity (MD) along the pyramidal tracts from the internal capsules down to the pyramids. A mixed model regression analysis was used to compare FA and MD between the ALS and control groups. RESULTS: FA showed a downward linear trend from the cerebral peduncles to the pyramids and was lower in the ALS group than controls at multiple levels of the corticospinal tract. At the internal capsules, FA was higher on the right. MD showed an upward trend, progressing caudally from the internal capsules to the pyramids. MD was higher at the level of the internal capsule in the ALS group, but caudally this difference was not maintained. No correlations were found between clinical markers of disability and water diffusion indices. CONCLUSIONS: These findings provide insights into the pathological processes of ALS. Differences in diffusion characteristics at different anatomical levels may relate to underlying tract architecture or the distribution of pathological damage in ALS. Further development may permit monitoring of progression and treatment of disease.

Adult↗

PubMed2003

Conversion to multiple sclerosis after a clinically isolated syndrome of the brainstem: cranial magnetic resonance imaging, cerebrospinal fluid and neurophysiological findings.

BACKGROUND AND AIM: Conversion to multiple sclerosis (MS) after optic neuritis and myelitis has been thoroughly studied; however, limited data are available regarding conversion to MS after a clinically isolated syndrome of the brainstem (CISB). The aim of this study was to investigate conversion to MS in patients with CISB. METHODS: Fifty-one patients with CISB were prospectively studied. Cranial magnetic resonance imaging (MRI), determination of oligoclonal bands (OBs) in the cerebrospinal fluid (CSF) and evoked potentials (EPs) were performed. Based on conversion to MS at follow-up, the sensitivity, specificity, accuracy and positive and negative predictive values of these tests were calculated. RESULTS: Clinically definite MS developed in 18 (35%) patients after a mean follow-up of 37 months. Paty's MRI criteria showed a sensitivity of 89%, a specificity of 52% and an accuracy of 65%; Fazekas' criteria showed a sensitivity of 89%, a specificity of 48% and an accuracy of 63%; Barkhof's criteria showed a sensitivity of 78%, a specificity of 61% and an accuracy of 67%. The presence of OBs in the CSF showed a sensitivity of 100%, a specificity of 42% and an accuracy of 63%. No differences for neurophysiological parameters were found between patients who did and those who did not convert to MS. CONCLUSION: Fulfilling Paty's, Fazekas' or Barkhof's MRI criteria and the presence of OBs in the CSF are associated with a higher risk of conversion to MS in patients with CISB. Determination of OBs in the CSF has the greatest sensitivity of all tests. Barkhof's MRI criteria have greater specificity (although less than previously published for mixed cohorts of clinically isolated syndromes) in predicting conversion to MS for CISB than either Paty's or Fazekas' criteria.

Adolescent↗

PubMed2003

Preliminary magnetic resonance study of the macromolecular proton fraction in white matter: a potential marker of myelin?

We report on a new quantitative magnetization transfer (MT) technique that allows for the in vivo estimation of the macromolecular proton fraction (f) and the bound pool T2 relaxation time (T2b), whilst permitting whole brain coverage. In this pilot study, five subjects with multiple sclerosis (MS) and five healthy controls were studied. Both f and T2b were significantly different between MS lesions and normal control white matter (WM). Relationships between f and T1 relaxation time [Spearmans rank correlation coefficient (r(s)) = -0.97, P < 0.001] and f and the magnetization transfer ratio (MTR; r(s) = 0.80, P < 0.001) were observed. Compared with MTR, f and T2b have the potential advantage of relative independence from MT acquisition protocol while offering more pathologically specific information. In particular, f may provide a more direct indication of myelin content in WM.

Adult↗

PubMed2003

Evidence-based measurement in multiple sclerosis: the psychometric properties of the physical and psychological dimensions of three quality of life rating scales.

The selection of measures of quality of life used in clinical trials of multiple sclerosis (MS) should be evidence-based. Head-to-head comparison of measures facilitates the selection of measures. The aim of the study was to compare the psychometric properties of the physical and psychological dimensions in three measures of quality of life to aid choice of the most appropriate scale for use in clinical trials of MS. One hundred and twenty-one people with MS (rehabilitation = 57; steroids = 64) completed a selection of health measures before and after treatment. The psychometric properties of three measures of physical function (MSIS-29 physical, SF-36 physical functioning, FAMS mobility) and three measures of psychological function (MSIS-29 psychological, SF-36 mental health, FAMS emotional well-being) were compared by examining data quality, scaling assumptions, acceptability, reliability, validity and responsiveness. Physical (0.63-0.71) and psychological (0.70-0.75) scales were substantially correlated indicating they measure related constructs. The MSIS-29 physical and psychological scales satisfied all criteria for internal consistency reliability (physical = 0.91; psychological = 0.89) and validity. The SF-36 physical scale had a notable floor effect (20%). The FAMS mobility scale had lower reliability (alpha = 0.78) compared to other measures. The MSIS-29 physical (effect size = 0.91) and psychological (effect size = 0.62) scales were the most responsive. In these three samples, the MSIS-29 had better measurement properties for combined physical and psychological health than the SF-36 and the FAMS.

Adult↗

PubMed2003

Diagnosis of MS: a comparison of three different clinical settings.

In order to compare a newly established diagnostic clinic with two existing clinical settings in the management of the diagnostic phase of multiple sclerosis (MS), a retrospective audit was performed over a 12-month period comparing the length of time, adherence to recently published standards and price charged in diagnosing MS in three different clinical diagnostic settings operating within the same hospital: a specifically designed demyelinating disease diagnostic clinic (DDC), a general neurology clinic (GNC) and an inpatient investigation unit (IIU). An audit tool was created to measure the standards advocated by the UK MS Society on management of the diagnostic phase of MS. The costing tool was the price charged to health authorities. A randomized retrospective case note and referral letter review method was used. The entry criterion was a confirmed diagnosis of MS documented in the medical notes following investigation during the period April 1999-April 2001. The time between referral and first appointment favoured the DDC with a mean time of 5.9 weeks, compared to 7.7 weeks for the GNC and 10.0 weeks for the IIU. The mean times between the first appointment and receipt of results were 4.7 weeks (DDC), 18.8 weeks (GNC) and 21.2 weeks (IIU). Prices ranged from pounds sterling 395-pounds sterling 790 (DDC), pounds sterling 95-pounds sterling 380 (GNC) and pounds sterling 1940-pounds sterling 2700 (IIU). This study suggests that the UK MS Society standards are achievable in most areas without excessive additional costs and provides evidence that the DDC offers a better service than other existing models.

Adult↗

PubMed2003

Disability in multiple sclerosis is related to normal appearing brain tissue MTR histogram abnormalities.

BACKGROUND: Magnetization transfer ratio (MTR) histogram analysis provides a global measure of disease burden in multiple sclerosis (MS). MTR abnormalities in normal appearing brain tissue (NABT) provide quantitative information on the extent of tissue damage undetected by conventional T2-weighted (T2W) magnetic resonance imaging (MRI). AIMS: 1) To compare the MTR histograms from NABT across a broad spectrum of relapse onset MS patients, including relapsing-remitting (RR) MS (including newly diagnosed and benign subgroups) and secondary progressive (SP) MS. 2) To determine the relationship between clinical disability and NABT MTR histograms. METHODS: 2D spin echo magnetization transfer imaging was performed on 70 RRMS and 25 SPMS patients and compared with 63 controls. MTR histograms were acquired for NABT after extracting lesions and cerebrospinal fluid (CSF). T2W images were used to measure the brain parenchymal fraction (BPF) and T2 lesion load. RESULTS: MS patients had a disease duration ranging from 0.5 to 37 years and an Expanded Disability Status Scale (EDSS) score ranging from 0 to 8.5. There was a significant decrease in NABT mean MTR (+/- standard deviation) compared with controls (33.07 pu +/- 1.06 versus 34.26 pu +/- 0.47; P < 0.001) with an effect size of 2.56. The reduction in NABT mean MTR varied among patient groups from 4.9% for SPMS, 3% for all RRMS, 2.7% for early RRMS and 2.5% for benign MS, compared with controls. NABT mean MTR correlated significantly with T2 lesion load (r = -0.82) and BPF (r = 0.58). EDSS score correlated with NABT mean MTR (r = -0.43), BPF (r = -0.33) and with T2 lesion load (r = 0.59). Multivariate analysis using NABT MTR peak height, T2 lesion load and BPF combined only accounted for 38% of the variance in the EDSS (r = 0.62; P < 0.001). Disease duration accounted for an additional 14% of variance in the EDSS (r = 0.72; P < 0.001). CONCLUSIONS: There is evidence of diffuse abnormalities in NABT in addition to global brain atrophy in relapse onset MS patients, including those with recently diagnosed RRMS and benign MS. The abnormalities are greatest in patients with the more disabling SPMS. Atrophy, NABT and lesion abnormalities are all partly correlated; the processes marked by these MR measures all contribute to disability in MS, providing complementary information relevant to the complex pathological processes that occur in MS.

Adult↗

PubMed2003

Towards a european network for multiple sclerosis trials (ENMST).

Quality standards for clinical studies in the field of multiple sclerosis (MS) have improved significantly, to the great benefit of patients. This development has been accompanied by soaring costs and ever increasing complexity, with industry-independent trials having become virtually impossible. We propose establishing a European network that would include expertise in all the relevant aspects of MS treatment trials. In a stepwise approach, all interested active centres across Europe should be recruited into the network, based on agreement upon common scientific standards and quality requirements. Three main goals are discussed: to facilitate identification of potentially useful agents for MS treatment; to establish protocols for the interaction between investigators and industry; and to identify common standards and a core set of data to allow for comparisons of MS trials. Collaboration with existing international organizations and institutions, especially the Sylvia Lawry Centre for MS Research, as well as with similar initiatives in North America and other parts of the world is envisaged.

Clinical Trials as Topic↗

PubMed2003

[Diagnosis of multiple sclerosis].

This article prepared by members of International Panel working on new diagnostic criteria of multiple sclerosis (MS) presents and discusses these criteria, which pay special attention to MRI as a method of confirmation of dissemination in space and in time, necessary for MS diagnosis. Also main problems of MS differential diagnosis are discussed as well as significance of other laboratory methods like evoked potentials and cerebrospinal fluid studies. Nevertheless the significance of clinical signs in MS diagnosis are decisive.

Acute Disease↗