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Alan J Thompson

Publications and source records attributed to Alan J Thompson.

63 records · Page 4Linked to original sources

Disability and lesion load in MS: a reassessment with MS functional composite score and 3D fast FLAIR.

The correlation between T2 lesion load (LL) detected on conventional MR sequences and disability assessed by the Expanded Disability Status Scale (EDSS) in multiple sclerosis (MS) is, at best, moderate. The present study was performed to determine whether the correlation between disability and LL is improved by (i) use of the more sensitive three-dimensional fast fluid-attenuated inversion recovery (3D-fast FLAIR) sequence; (ii) application of the newly devised MS functional composite (MSFC) score. Forty-one patients with clinically definite or probable MS were studied. All had been followed prospectively for 14 years since their first symptom. EDSS and MSFC score were assessed. Imaging was performed with 3D-fFLAIR, fast spin-echo (FSE), and T1 weighted SE sequences. 3D-fFLAIR detected a 34% higher LL than FSE, but did not improve the correlation between T2 LL and EDSS (r = 0.51 and r = 0.53); the correlation was stronger with T1 LL (r = 0.57). The MSFC score did not significantly correlate with T2 LL or T1 LL. The robust correlation in this cohort between T2 LL and EDSS may reflect the homogeneous disease duration and the wide spread of disability. This correlation was not improved by the increased detection of T2 lesions with the 3D-fFLAIR sequence. The stronger correlation between T1 LL with EDSS is consistent with the finding that this subgroup of lesions represent areas of more severe tissue damage. The MSFC score did not improve the clinico-radiological paradox that is found in MS, despite including information on cognitive function.

Adolescent↗

Monitoring disease activity and progression in primary progressive multiple sclerosis using MRI: sub-voxel registration to identify lesion changes and to detect cerebral atrophy.

OBJECTIVE: To explore the potential usefulness of two new magnetic resonance imaging (MRI) analysis techniques for assessment of progressive cerebral atrophy and T2 lesion activity in primary progressive multiple sclerosis (PPMS), and thereby assess the relationship between MRI activity and atrophy in this patient group. BACKGROUND: Measurements of cerebral atrophy and net change in T2 lesion volumes are currently used as surrogate markers of disease progression in multiple sclerosis (MS). However, manual implementation of these techniques is time-consuming and the pathological specificity of T2 lesion change is low. Advances in serial scan registration have facilitated the development of a new, fully-automated technique to measure cerebral volume (SIENA; Structural Image Evaluation, using Normalisation, of Atrophy), and a technique to measure the total new T2 lesion volume selectively (MRI difference imaging). METHOD: SIENA measures changes in cerebral size based on sub-voxel detection of shifts in edge contours. The lesion difference imaging method measures differences in lesion volumes over time as defined by a semi-automated outlining technique. The two new methods were validated against the T2 lesion volume contour technique and a previously described measure of partial brain volume (which uses six slices centred on the presumed area of greatest change around the lateral ventricles). All were applied to serially acquired MR images from a cohort of 39 patients with PPMS, who also underwent scoring on the expanded disability status scale (EDSS) twice, two years apart. RESULTS: The two measures reflecting cerebral atrophy correlated strongly (r = 0.58, p < 0.001). T2 lesion load measurements using the two techniques correlated very highly (r = 0.999, p < 0.001). 91% of the total new T2 lesion volume was from enlargement of pre-existent lesions and only 9 % from new, discrete, lesions. No relationship was seen between the traditional measure of net gain in T2 lesion load and either measure of atrophy. However, the fully-automated measure of total new T2 load correlated with both measures of atrophy (SIENA technique, r= -0.37, p= 0.02; six slice measure, r = -0.41, p = 0.01). There was no relationship between the MRI measures and changes in the EDSS. CONCLUSION: Both of the new image analysis techniques appear to be promising as sensitive markers for disease progression in PPMS. The correlation of total new T2 lesion volume with the progression of cerebral atrophy (which is known to be a consequence of axonal loss in progressive disease), compared with a lack of correlation with the traditional net gain in T2 lesion load is interesting and suggests that the total new T2 lesion volume may ultimately be the most useful measure.

Adult↗

The relationship between lesion and normal appearing brain tissue abnormalities in early relapsing remitting multiple sclerosis.

BACKGROUND: In multiple sclerosis (MS), pathological changes have been found both in macroscopic lesions and normal appearing tissue. Magnetisation transfer ratio (MTR) and T1 relaxation time are abnormal in normal appearing tissues in established MS. This study used these MR techniques in early MS to study normal appearing tissues and lesions. The purpose was to determine whether abnormalities are already detectable in normal appearing tissues in early MS, and if so how they correlate with lesion characteristics. METHODS: Twenty two patients with early relapsing remitting (RR) MS (median disease duration 2 years, range 7 months-3 years) and 11 age-matched controls were studied. MTR and T1 relaxation times were measured in 9 regions of normal appearing white matter (NAWM) and 7 of normal appearing grey matter (NAGM). Gadolinium enhancing, T1-hypointense and T2 lesion loads were measured in all patients. RESULTS: When all regions were combined, there was a significant difference between patient and control NAWM for both T1 and MTR; T1 was abnormal in 6/9 and MTR in 3/9 NAWM regions. Global assessment of NAGM revealed a significant difference between patients and controls for Ti but not for MTR; T1 was significantly abnormal only in frontal NAGM. There was no significant correlation between NAWM T1 or MTR and any of the lesion load measurements. CONCLUSIONS: This study reveals quantitative MR abnormalities in both NAWM and NAGM in early RR MS, with more extensive changes in the former. The lack of correlation between NAWM and lesion abnormalities suggests that they have developed by at least partly independent mechanisms. T1 may be more sensitive than MTR in detecting subtle pathological changes in NAWM and NAGM.

Adult↗

Measurement of atrophy in multiple sclerosis: pathological basis, methodological aspects and clinical relevance.

MRI methods are widely used to follow the pathological evolution of multiple sclerosis in life and its modification by treatment. To date, measures of the number and volume of macroscopically visible lesions have been studied most often. These MRI outcomes have demonstrated clear treatment effects but without a commensurate clinical benefit, suggesting that there are other aspects of multiple sclerosis pathology that warrant investigation. In this context, there has been considerable interest in measuring tissue loss (atrophy) as a more global marker of the adverse outcome of multiple sclerosis pathology, whether it arises in macroscopic lesions or in the normal appearing tissues. An International Workshop recently considered the measurement of atrophy in multiple sclerosis and provided the basis for this review. Brain white matter bulk consists predominantly of axons (46%) followed by myelin (24%), and progressive atrophy implies loss of these structures, especially axons, although variable effects on tissue volumes may also arise from glial cell proliferation or loss, gliosis, inflammation and oedema. Significant correlations found between brain volume and other putative MR neuronal markers also indicate that atrophy reflects axonal loss. Numerous methods are available for the measurement of global and regional brain volumes and upper cervical cord cross-sectional area that are highly reproducible and sensitive to changes within 6-12 months. In general, 3D-T(1)-weighted acquisitions and largely automated segmentation approaches are optimal. Whereas normalized volumes are desirable for cross-sectional studies, absolute volume measures are adequate for serial investigation. Atrophy is seen at all clinical stages of multiple sclerosis, developing gradually following the appearance of inflammatory lesions. This probably reflects both inflammation-induced axonal loss followed by Wallerian degeneration and post-inflammatory neurodegeneration that may be partly due to failure of remyelination. One component of atrophy appears to be independent of focal lesions. Existing immunomodulatory therapies have had limited effects on progressive atrophy, concordant with their modest effects on progressive disability. Atrophy provides a sensitive measure of the neurodegenerative component of multiple sclerosis and should be measured in trials evaluating potential anti-inflammatory, remyelinating or neuroprotective therapies.

Atrophy↗

Progress in neurorehabilitation in multiple sclerosis.

Despite being acknowledged as an important component in the overall management of multiple sclerosis, the relatively few evaluative studies in symptomatic treatment and rehabilitation have meant that the evidence base is still poor. The encouraging work on health outcome measures, together with an improved understanding of the mechanisms underlying disability, provide a useful base for improving the lot of patients with multiple sclerosis. These advances need to be associated with improved models of care which provide comprehensive and accessible services throughout the course of the disease.

Ataxia↗

Quality of life measurement after stroke: uses and abuses of the SF-36.

BACKGROUND AND PURPOSE: The Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) is widely used to measure health status after stroke. However, a fundamental assumption for its valid use after stroke has not been comprehensively tested: is it legitimate to generate scores for 8 scales and 2 summary measures using the standard algorithms? We tested this assumption. METHODS: SF-36 data from 177 people after stroke were examined (71% male; mean age, 62). We tested 6 scaling criteria to determine the legitimacy of generating the 8 SF-36 scale scores using Likert's method of summed ratings, and we tested 2 scaling criteria to determine the appropriateness of the standard SF-36 algorithms for weighting and combining scale scores to generate 2 summary measures (physical and mental). RESULTS: Scaling assumptions were fully satisfied for 6 of the 8 scales, but 3 of these 6 scales had notable floor and/or ceiling effects. Assumptions for generating 2 SF-36 summary measures were not satisfied. CONCLUSIONS: In this sample, 5 of the 8 SF-36 scales had limited validity as outcome measures after stroke, and the reporting of physical and mental summary scores was not supported. Results raise questions about the use of the SF-36 in stroke, and the SF-12 that is developed from it, and highlight the importance of testing scaling assumptions when applying existing scales to new populations.

Adult↗

Integrated care pathways: disease-specific or process-specific?

BACKGROUND/AIM: conventional teaching on integrated care pathways (ICP) suggests that they have to be specific both to a particular setting and to a specific diagnosis. We wished to explore the potential for a generic process-based care pathway. STUDY DESIGN: we evaluated three different, disease-specific ICPs in use on a neurological rehabilitation unit to identify prompts common to and differing between them. Variance types and goal outcomes in all three diagnostic groups were compared. RESULTS: 93% of prompts on the care pathway were common to all three diagnostic groups. The prompts that differed were unique to each diagnostic group and provided important guidelines about management. CONCLUSION: in neurorehabilitation, where the process of multidisciplinary care is well defined, it is possible to develop a process-based ICP. Process-based ICPs may not be unique to rehabilitation but may also be relevant to other settings in which patients with differing diagnoses share similar needs.

Adolescent↗

Magnetic resonance imaging in primary progressive multiple sclerosis.

Ten to fifteen percent of patients with multiple sclerosis (MS) have a condition that is progressive from onset without a preceding relapsing-remitting phase: this is known as primary progressive multiple sclerosis (PPMS). Patients with PPMS tend to be older, often present with motor symptoms and, in contrast to relapsing MS, are as likely to be male as female. The conventional magnetic resonance imaging (MRI) characteristics of PPMS include a tendency to lower lesion loads and lower rate of new lesion formation. In common with relapsing MS, the relation between conventional MRI abnormalities and clinical condition is poor. Studies using newer MRI techniques, such as magnetization transfer imaging (MTI), diffusion-weighted imaging (DWI), magnetic resonance spectroscopy (MRS), and functional MRI (fMRI), have also been carried out. These techniques are sensitive to a wider range of abnormalities within tissue, and their increased pathological specificity may be helpful in clarifying the underlying pathology of the condition.

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