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Biomedical subjects

A J Thompson

Publications and source records attributed to A J Thompson.

At least 181 records · Page 10Linked to original sources
PubMed1999

Cognitive function in primary progressive and transitional progressive multiple sclerosis: a controlled study with MRI correlates.

The relative rarity of primary progressive (PP) and transitional progressive (TP) multiple sclerosis has meant that little documentation of cognitive function in such patients is currently available. The aim of this study was to investigate the cognitive skills of patients with PP and TP multiple sclerosis relative to matched healthy controls, and to examine the relationship of this impairment to MRI parameters. Sixty-three patients (43 PP, 20 TP) were individually matched with healthy controls, who undertook the same cognitive tasks as the patient group. The neuropsychological assessment comprised Rao's brief repeatable battery, a reasoning test, and a measure of depression. Patients also underwent T1- and T2-weighted brain MRI. These patients were taken from a larger cohort (158 PP, 33 TP) in whom it had been demonstrated that the re were no significant differences between the mean scores of the PP and TP groups on any of the cognitive variables. The 63 patients were therefore taken as one group for comparison with the healthy controls. These patients performed significantly worse than the controls in tests of verbal memory, attention, verbal fluency and spatial reasoning. An impairment index was constructed and applied to the patient data. This correlated modestly with T2-lesion load (r = 0.45, P = 0.01), T1-hypointensity load (r = 0.45, P = 0.01) and cerebral volume (r = -0.35, P = 0.01). Thus, PP and TP multiple sclerosis patients demonstrate significant cognitive dysfunction when compared with matched healthy controls. The relationship between this impairment and MRI parameters is moderate, suggesting that cognitive dysfunction in PP and TP multiple sclerosis has a complex and multifactorial aetiology, which is not adequately explained by pathology as demonstrated on conventional MRI.

Adult↗
PubMed1999

Myometrial constitutive nitric oxide synthase expression is increased during human pregnancy.

Nitric oxide (NO), derived from L-arginine by the action of nitric oxide synthase (NOS), is a mediator of many diverse biological activities, including vasodilation, neurotransmission and inhibition of platelet adhesion. A role for NO in the maintenance of rat and rabbit pregnancy is supported by a variety of studies. A recent study in women demonstrated that myometrial inducible NOS (iNOS) expression was greater in the early third trimester than either the late third trimester or in the non-pregnant condition, suggesting that increased iNOS expression is involved in the maintenance of human pregnancy. Constitutive NOS (cNOS) expression was not determined. The aim of this study was to compare constitutive NOS (both eNOS and bNOS) expression in the human non-pregnant uterus, preterm pregnant uterus (25-34 weeks gestation) and term pregnant uterus (>37 weeks gestation) using immunohistochemistry and Western blotting. Preterm pregnant samples were taken from women with a variety of pathologies necessitating early delivery. We found that eNOS and bNOS protein concentrations were greater in the preterm pregnant myometrium than non-pregnant myometrium. eNOS, but not bNOS, protein concentration was lower in myometrial samples obtained at term compared with those obtained preterm. We conclude that the constitutive isoforms of NOS are also up-regulated in human pregnancy and may play a role in the maintenance of myometrial quiescence.

Blotting, Western↗
PubMed1999

Measuring change in disability after inpatient rehabilitation: comparison of the responsiveness of the Barthel index and the Functional Independence Measure.

BACKGROUND: The importance of evaluating disability outcome measures is well recognised. The Functional Independence Measure (FIM) was developed to be a more comprehensive and "sensitive" measure of disability than the Barthel Index (BI). Although the FIM is widely used and has been shown to be reliable and valid, there is limited information about its responsiveness, particularly in comparison with the BI. This study compares the appropriateness and responsiveness of these two disability measures in patients with multiple sclerosis and stroke. METHODS: Patients with multiple sclerosis (n=201) and poststroke (n=82) patients undergoing inpatient neurorehabilitation were studied. Admission and discharge scores were generated for the BI and the three scales of the FIM (total, motor, and cognitive). Appropriateness of the measures to the study samples was determined by examining score distributions, floor and ceiling effects. Responsiveness was determined using an effect size calculation. RESULTS: The BI, FIM total, and FIM motor scales show good variability and have small floor and ceiling effects in the study samples. The FIM cognitive scale showed a notable ceiling effect in patients with multiple sclerosis. Comparable effect sizes were found for the BI, and two FIM scales (total and motor) in both patients with multiple sclerosis and stroke patients. CONCLUSION: All measures were appropriate to the study sample. The FIM cognitive scale, however, has limited usefulness as an outcome measure in progressive multiple sclerosis. The BI, FIM total, and FIM motor scales show similar responsiveness, suggesting that both the FIM total and FIM motor scales have no advantage over the BI in evaluating change.

Activities of Daily Living↗
PubMed1999

Does the extent of axonal loss and demyelination from chronic lesions in multiple sclerosis correlate with the clinical subgroup?

OBJECTIVE: To determine non-invasively the relation between the degree of axonal loss and the extent of demyelination in chronic lesions visible on MRI in patients with different subgroups of clinically definite multiple sclerosis using (1)H magnetic resonance spectroscopy ((1)H MRS) and magnetisation transfer imaging (MT). Conventional MRI is unable to differentiate between the various pathological processes occurring in the multiple sclerosis lesion. There are, however, newer MR techniques which show promise in this respect. METHODS: (1)H MRS and MT were performed in 18 patients with clinically definite multiple sclerosis who had a wide range of disability and disease duration. RESULTS: A significant correlation was found between a reduction in the concentration of N-acetyl aspartate (NAA; an in vivo marker of axonal loss or dysfunction) and a reduction in MT ratio (a probable marker of demyelination) in patients who had entered the secondary progressive stage of the disease. Patients with minimal disability after a disease duration of greater than 10 years-so called benign multiple sclerosis-showed a relative preservation of NAA and MT. CONCLUSIONS: Because a reduction in MT seems to be a relative marker for demyelination and a reduction of NAA from chronic lesions is indicative of axonal loss, this study supports the hypothesis that demyelination and axonal loss occur in the same chronic multiple sclerosis lesions. In addition, the degree of axonal loss and demyelination correlates with clinical heterogeneity.

Aspartic Acid↗
PubMed1999

Correlates of executive function in multiple sclerosis: the use of magnetic resonance spectroscopy as an index of focal pathology.

Proton magnetic resonance spectroscopy (MRS) was performed in a group of patients with multiple sclerosis (MS) and matched control subjects to examine the relationship between frontal lobe pathology and performance on tests of executive function. The N-acetyl aspartate/creatine ratio (NAA/Cr) was significantly reduced in frontal lesions and/or normal-appearing white matter in the patient group compared with the control group, but choline/creatine ratios did not differ. Although MRS abnormalities and executive deficits were not correlated for MS patients as a group, a few patients with more severe abnormalities of NAA/Cr ratio performed worse than other patients on the spatial working memory test, suggesting that subtle frontal neuropathological abnormalities detected by MRS may contribute to executive deficits. Further investigation is warranted to determine the value of MRS as an index of the pathophysiological processes leading to cognitive deficit.

Adult↗
PubMed1999

Multiple sclerosis: a preliminary study of selected variables affecting rehabilitation outcome.

PROBLEM: The diversity of physical and cognitive impairments seen in progressive multiple sclerosis (MS), make it difficult to identify the factors that influence neurorehabilitation outcome. Improvements in a motor disability scale must be considered in the context of the patient's physical and cognitive starting points, if the process of neurorehabilitation is to be properly understood. METHOD: Data was collected from 38 patients (mean age 41 years, 16 men and 22 women) with clinically definite MS (of whom all but one were in the progressive phase of the disease), who were consecutively admitted to a neurorehabilitation unit. Patients' physical disability was assessed on the motor scale of the Functional Independence Measure (FIM) on admission and discharge. Cognitive and neurological assessments were completed on admission. The cognitive battery comprised the WAIS-R, NART, RMT, CVLT CMT, GNT, GDA, and VOSP (some in short form). Emotional measures were the STAI, STAXI and BDI. RESULTS: The mean improvement on the FIM was 6 points. A multiple regression analysis was performed to determine which cognitive and neurological variables related to reduced disability after neurorehabilitation. To take account of each patient's starting point, the model included their FIM admission score. This variable, together with vocabulary skills and cerebellar function accounted for 57% of the variance in the patients' improvements. These results suggest that verbal intelligence and cerebellar function are influential in determining rehabilitation outcome. Although these findings will be unsurprising to clinicians, this is the first quantitative demonstration of these effects.

Adult↗
PubMed1999

Measuring handicap in multiple sclerosis.

Handicap, shortly to be renamed participation, is a well defined though somewhat neglected entity which addresses an important aspect of the impact disease has on the individual. It is particularly relevant in Multiple Sclerosis (MS) which has such a major impact on issues such as employment, relationships, transport and social integration. Few validated measuring tools exist, and the generic London Handicap Scale is probably the best currently available but is only appropriate for group comparison. Handicap should be monitored in MS and is particularly appropriate in the evaluation of rehabilitation strategies.

Disability Evaluation↗
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↗
PubMed1999

Quantitative MRI in patients with clinically isolated syndromes suggestive of demyelination.

OBJECTIVE: To assess the long-term predictive value of quantitative lesion load measurement on brain MRIs in patients after a 10-year follow-up who presented initially with a clinically isolated syndrome of the optic nerve, brainstem, or spinal cord. BACKGROUND: Quantitative MRI measurement is being used in treatment trials as a surrogate marker in MS, but there is a lack of long-term MRI follow-up data in assessing the natural course of the disease from the earliest stages. METHODS: Using a semiautomated threshold technique, the total lesion volume (TLV), the course of the disease, and disability were assessed in 58 patients at onset and after 5 and 10 years. RESULTS: The TLV at presentation correlated significantly (r = 0.81, p = 0.0001) with the TLV and also with the Expanded Disability Status Scale (EDSS) score (r = 0.45, p = 0.001) at 10-year follow-up. In contrast there was no correlation of the TLV at 5 years with subsequent change in EDSS score over the next 5 years (r = 0.18, p = 0.12). The change in TLV over the first 5 years in patients who developed clinically definite MS (CDMS) differed significantly according to the type of disease course (relapsing-remitting with disability, secondary progressive, or benign) manifesting at 10-year follow-up. CONCLUSION: Quantification of changes detected by T2-weighted brain MRI at the earliest clinical stages is strongly predictive of the subsequent development of CDMS as well as the clinical course and level of disability 10 years later.

Adolescent↗
PubMed1998

Improved imaging of the spinal cord in multiple sclerosis using three-dimensional fast spin echo.

We report assessment of a new three-dimensional fast spin echo (3D FSE) sequence in ten patients with clinically definite multiple sclerosis, comparing it with standard 2D FSE, and in ten normal controls. We saw 29 focal lesions on the 2D images and 53 on the 3D FSE images (P = 0.05); none were seen in controls. Lesion length was significantly smaller on the 3D FSE than on to the 2D FSE images (3D: 1.36; 2D 2.0; P = 0.03). This may relate in part to separation into several lesions on the 3D images of confluent abnormal signal seen on 2D and in part to detection of small lesions missed by the thicker 2D FSE slices (3 mm compared to 1.5 mm). The 3D FSE sequence looks promising in improving spinal cord imaging.

Adult↗
PubMed1998

Multiple sclerosis: assessment of disability and disability scales.

Attempting to measure the impact of multiple sclerosis (MS) on the individuals patients has become a major issue stimulated by both the emergence of new therapeutic agents and the increasing demand to incorporate the patient's perspective. Disability has been the main focus. Recently, new disability scales have been developed and generic scales evaluated in an attempt to replace or complement the constantly used and much criticized Expanded Disability Status Scale (EDSS). There is, however, the growing realization that it is important to incorporate broader aspects of disease input such as are contained within the concepts of health-related quality of life. Current scales in this area are limited in either their scientific soundness and/or clinical usefulness, and it may be appropriate to consider the development of a new MS-specific measure of disease impact for use in clinical trials.

Disability Evaluation↗
PubMed1998

Multiple sclerosis: rehabilitation measures.

The importance of rehabilitation in the management of multiple sclerosis is now well appreciated as is the need to demonstrate benefit through the appropriate use of scientifically sound outcome measures and integrated care pathways. Encouraging results are emerging from a number of recent studies. However, there remains a need to provide and evaluate comprehensive service provision through the identification of need and the formulation of agreed standards of care.

Delivery of Health Care↗
PubMed1998

Secondary progressive multiple sclerosis: the relationship between short-term MRI activity and clinical features.

We report the findings in 60 patients with secondary progressive multiple sclerosis who had monthly brain MRI studies for 4 months (one baseline and three follow-up scans). The purpose was to define the short-term MRI natural history in a large cohort with secondary progressive disease and to ascertain its relationship with other clinical and MRI features. The patients were participating in either a natural history study or the placebo arm or non-treatment phase of a therapeutic trial. The cohort had clinical features typical of secondary progressive disease: thus, all had moderate or severe locomotor disabilities [Expanded Disability Status Scale (EDSS), score 3.5-8], with a median disease duration of 12 years. There was equal representation of males and females. During the 3 months of follow-up there was a total of 362 new enhancing lesions seen in 42 patients, and there were 24 relapses in 20 patients. There was no correlation between new enhancing lesions and age at study entry, age of disease onset, gender disease duration or EDSS, but there was a strong correlation with the number of enhancing lesions on the baseline scan (r = 0.65, P < 0.0001) and subsequent activity. There was a non-significant trend for higher numbers of new enhancing lesions in those having relapses during the 3 months of scanning (P = 0.14) or in the preceding 6 months (P = 0.06). The 34 patients who did not relapse in either period had significantly fewer new active lesions (P = 0.02) than those who relapsed at some stage during the 9 months. Nevertheless, considerable activity was seen in the non-relapsing cohorts: there was a mean of 3.5 (median 2) new enhancing lesions in those not relapsing during the 3 month study, and 5.5 (median 2) in those not relapsing in the previous 6 months. We conclude that short-term MRI activity is generally high in secondary progressive disease, confirming a useful role for the technique in exploratory trials. Further work should concentrate on elucidating the mechanisms of secondary progression by longer term follow-up studies of larger cohorts using multiple MRI and clinical measurements.

Adult↗
PubMed1998

The prognostic value of brain MRI in clinically isolated syndromes of the CNS. A 10-year follow-up.

A definitive diagnosis of multiple sclerosis cannot be made at presentation on patients with a clinically isolated syndrome of the optic nerve, spinal cord or brainstem suggestive of demyelination, as dissemination in time is not established. To determine the long-term risk of abnormalities on brain MRI for the development of multiple sclerosis and disability we performed a 10-year follow-up on 81 such patients who had T2-weighted brain MRI at presentation. Initial brain MRI was abnormal in 54 (67%). Follow up of those patients with an abnormal MRI revealed progression to clinically definite multiple sclerosis in 45 out of 54 (83%), of whom 11 (20%) had relapsing/remitting disease (EDSS > 3), 13 (24%) secondary progressive and 21 (39%) benign (relapsing/remitting with EDSS < or = 3) disease. For those with a normal MRI progression to clinically definite multiple sclerosis occurred in only three out of 27 (11%), all benign. There was a significant relationship between the number of lesions at presentation and both EDSS (r = 0.45, P < 0.001) and the type of disease at follow-up (P < 0.0001). Brain MRI at presentation with a clinically isolated syndrome is predictive of the long-term risk of subsequent development of multiple sclerosis, the type of disease and extent of disability.

Adolescent↗
PubMed1998

An open-labelled clinical and electrophysiological study of 3,4 diaminopyridine in the treatment of fatigue in multiple sclerosis.

We studied the electrophysiological parameters of motor performance in eight patients with multiple sclerosis and troublesome fatigue, before and after treatment with 3,4-diaminopyridine. Symptomatic fatigue was evaluated by the Krupp Fatigue Severity Score and motor performance of adductor pollicis by transcranial magnetic stimulation, rapid voluntary movements and a fatiguing exercise test of a sustained 45-s isometric contraction. The motor tests revealed baseline abnormal motor function and substantial central fatigue. After a 3-week course of 3,4-diaminopyridine (25-60 mg/day), six out of the eight patients reported substantial improvement in fatigue and the group showed slightly less fatigue on the exercise test. Other electrophysiological tests of motor function were unchanged. The findings suggest that 3,4-diaminopyridine may play a role in the symptomatic treatment of fatigue in multiple sclerosis. However, the mechanism behind such a benefit in fatigue remains unclear and the discrepancy between subjective and more objective responses underlines the probable multifactorial nature of the pathogenesis of this symptom in multiple sclerosis.

4-Aminopyridine↗
PubMed1998

Central motor conduction time in progressive multiple sclerosis. Correlations with MRI and disease activity.

The purpose of this study was to relate abnormalities of motor conduction time to the presence of spinal cord MRI lesions in progressive multiple sclerosis and to investigate the relationship between changes in motor conduction over time and clinical and MRI changes. Central motor conduction time (CMCT), serial MRI of the brain and spinal cord, and clinical evaluations were carried out in 20 patients with primary and secondary progressive multiple sclerosis. CMCT was carried out at the beginning and end of the study whilst the clinical and MRI examinations occurred at monthly intervals for 12 months. Median CMCT to abductor pollicis brevis was 14.8 ms (range 8.8-27.4 ms). The response latency to tibialis anterior correlated with disability measured on the Expanded Disability Status Scale. Latencies to upper limb muscles correlated with cervical MRI lesion load and the presence of atrophy of the cervical cord. Over the 12-month study period, 15 of 19 patients deteriorated clinically. However, an increase in motor response latencies occurred only in the four patients who had developed new cord lesions. The results suggest that prolonged CMCT is related to spinal cord lesion load and that, over time, changes in the CMCT occur only when spinal cord lesion load increases. Clinical change in progressive multiple sclerosis may therefore occur without either the development of new lesions on MRI scans or an increase in motor conduction time. This suggests that clinical deterioration in these patients may occur by a mechanism other than increasing demyelination. This may be progressive axonal degeneration.

Adult↗