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S M Leary

Publications and source records attributed to S M Leary.

25 records · Page 2Linked to original sources
PubMed2000

Current management of multiple sclerosis.

Multiple sclerosis is a complex disease which presents a unique challenge in clinical management. This decade has seen the advent of new therapies which are partially effective in modifying the disease course. However, current therapies have no impact on existing neurological deficits and so supportive measures, symptomatic treatment and comprehensive rehabilitation remain at the core of management. Historically clinical practice has often been empirical but management should now be evidence-based and guided by consensus opinion if improvements in care are to be made.

Acute Disease↗
PubMed1999

Problems in designing and recruiting to therapeutic trials in primary progressive multiple sclerosis.

Patients with primary progressive multiple sclerosis have atypical clinical and magnetic resonance imaging (MRI) characteristics which present unique problems in designing and recruiting to therapeutic trials. The first randomised controlled therapeutic trial specifically for primary progressive multiple sclerosis is now underway. Although only an exploratory phase II study, it has provided further insight into difficulties in diagnosis, classification and choice of clinical and MRI outcome measures. Patients with primary progressive multiple sclerosis have a wide differential diagnosis and do not readily conform to the Poser criteria. They may therefore present diagnostic uncertainty, particularly as their classification often relies on a retrospective history. This was highlighted during the recruitment to this study of interferon-beta1a. Of the 138 patients referred with a definite diagnosis of primary progressive multiple sclerosis only 50 were enrolled in the study. Of the 88 patients not included, 50% either did not have primary progressive multiple sclerosis, or the diagnosis was not secure. Outcome measures pose particular problems. Clinically the focus must be on progression, and the measure should be both responsive and reliable. In relation to MRI, the currently recommended measures for therapeutic trials in relapsing/remitting and secondary progressive multiple sclerosis show little change in primary progressive multiple sclerosis, and therefore more pathologically specific MRI measures are required. Strict clinical guidelines and further developments in clinical and MRI measures are required to facilitate future therapeutic trials in primary progressive multiple sclerosis.

Brain↗
PubMed1999

1H magnetic resonance spectroscopy of normal appearing white matter in primary progressive multiple sclerosis.

Recent magnetic resonance imaging (MRI) and pathological studies have indicated that axonal loss is a major contributor to disease progression in multiple sclerosis. 1H magnetic resonance spectroscopy (MRS), through measurement of N-acetyl aspartate (NAA), a neuronal marker, provides a unique tool to investigate this. Patients with primary progressive multiple sclerosis have few lesions on conventional MRI, suggesting that changes in normal appearing white matter (NAWM), such as axonal loss, may be particularly relevant to disease progression in this group. To test this hypothesis NAWM was studied with MRS, measuring the concentration of N-acetyl derived groups (NA, the sum of NAA and N-acetyl aspartyl glutamate). Single-voxel MRS using a water-suppressed PRESS sequence was carried out in 24 patients with primary progressive multiple sclerosis and in 16 age-matched controls. Ratios of metabolite to creatine concentration (Cr) were calculated in all subjects, and absolute concentrations were measured in 18 patients and all controls. NA/Cr (median 1.40, range 0.86-1.91) was significantly lower in NAWM in patients than in controls (median 1.70, range 1.27-2.14; P = 0.006), as was the absolute concentration of NA (patients, median 6.90 mM, range 4.62-10.38 mM; controls, median 7.77 mM, range 6.60-9.71 mM; P = 0.032). There was no significant difference in the absolute concentration of creatine between the groups. This study supports the hypothesis that axonal loss occurs in NAWM in primary progressive multiple sclerosis and may well be a mechanism for disease progression in this group.

Adult↗
PubMed1999

Reproducibility of magnetic resonance imaging measurements of spinal cord atrophy: the role of quality assurance.

A sensitive magnetic resonance imaging (MRI) method to measure spinal cord cross-sectional area with the potential to monitor disease progression has recently been developed. As changes in cord area due to disease are usually small, assessment of the reliability of the methodology is essential in serial studies of spinal cord atrophy. The aim of this study was to institute and evaluate a protocol of quality assurance to determine long-term reproducibility of serial studies. Serial MRI of the spinal cord was carried out in five healthy volunteer controls over 1 year. Cross-sectional spinal cord areas were measured in a total of 46 scans. The mean coefficient of variation of all subjects over one year was 1.35%. The intra-observer coefficient of variation for same scan analysis was 0.63%. This study has confirmed high reliability of our serial data over one year and the on-going quality assurance protocol enables continuing evaluation of the reproducibility of results in serial studies. Quality assurance is an essential and practical component of all serial MRI studies, without which the clinical implications of change cannot be reliably evaluated.

Atrophy↗
PubMed1999

Magnetisation transfer of normal appearing white matter in primary progressive multiple sclerosis.

Patients with primary progressive multiple sclerosis may develop severe disability despite a paucity of lesions on conventional magnetic resonance imaging, raising the possibility that intrinsic changes in normal appearing white matter (NAWM) contribute to disability. This study has measured magnetisation transfer ratio (MTR), an index of tissue damage, of NAWM in 52 patients with primary progressive multiple sclerosis and 26 healthy controls. Absolute values of MTR were obtained from the genu of the corpus callosum and pons, and mean values were calculated from bilateral regions in the centrum semiovale, frontal white matter, parieto-occipital white matter and posterior limb of the internal capsule. The median MTR was lower in all regions in patients compared to controls. Median values (per cent units) were significantly lower in corpus callosum (39.73 vs 40.63; P=0.01), frontal white matter (39.11 vs 39.59; P=0.01) and centrum semiovale (37.21 vs37.82; P<0.05). This study has demonstrated small but widespread decreases in MTR in NAWM in primary progressive multiple sclerosis supporting the hypothesis that there are intrinsic changes in NAWM which may contribute to disability in this patient group.

Adult↗
PubMed1998

Spinal cord atrophy and disability in MS: a longitudinal study.

OBJECTIVE: To assess whether it is possible to measure changes in cord cross-sectional area during a 1-year period in patients with MS reliably. BACKGROUND: Involvement of the spinal cord in MS is extremely common and an important element in the development of disability. Although little relation has been shown between the cord lesion load and disability, a strong correlation between spinal cord atrophy and the expanded disability status scale (EDSS) has been demonstrated in cross-sectional studies. METHOD: A highly reproducible semiautomated technique that measures the cross-sectional area of the cord at the C2 level was applied to 13 healthy control subjects and 28 patients serially. RESULTS: This study confirms that patients have significantly smaller cords than control subjects at baseline (control subjects: mean 80.95 mm2, patients: mean 71.25 mm2, p = 0.01) and demonstrates that patients have a significant loss in cord cross-sectional area during 12 months, which was not seen in control subjects (p < 0.001). This reduction in cord size was most marked in the primary progressive patients who had a mean cord cross-sectional area loss of 3.52 mm2 (5.2%) and least in the secondary progressive (-0.26 mm2, 0.7%) and benign patients (-0.41 mm2, 0.8%). The baseline cord cross-sectional area correlated strongly with the EDSS (r = -0.52, p = 0.005) and with disease duration (r = -0.75, p < 0.001); however, there was no significant difference in cord area (p = 0.69) or change in cord area (p = 0.51) between those patients with a definite increase in EDSS and those without. CONCLUSION: This study demonstrates, for the first time, that it is possible to measure changes in cord cross-sectional area over time. The serial measurement of spinal cord atrophy may thus make an important contribution to the evaluation of therapeutic efficacy, especially in primary progressive disease.

Adult↗