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Biomedical subjects

Alan J Thompson

Publications and source records attributed to Alan J Thompson.

At least 55 records · Page 3Linked to original sources

Rehabilitation of the cancer patient: experience in a neurological unit.

We performed a retrospective review of all patients admitted to a neurological rehabilitation unit over a 5-year period to identify the benefits and problems associated with inpatient rehabilitation of patients with a life-limiting illness. Twenty-one patients (14 men; mean age 54 years) with primary or nonprimary neurological malignancy resulting in disability were studied. For each patient the following data was extracted: gender, age, diagnosis, source of referral, mechanism of disability, prognosis at time of referral, length of inpatient stay, disability on admission and discharge, and the place of discharge. All patients made functional gains, and all but 2 were discharged home. One patient died and 4 required readmission to an acute unit because of worsening discomfort or debility within a month of discharge. Patients with life-limiting illness resulting in neurological disability can benefit from inpatient rehabilitation. Optimal management of such patients demands careful liaison with palliative care teams.

Adult↗

Overview of London trial of intramuscular interferon-beta Ia in primary-progressive multiple sclerosis.

This short monograph describes the rationale, design and outcome of a pilot study of beta interferon in patients with primary progressive MS. A total of 50 patients were studied for 2 years using a randomized, double-blinded, placebo-controlled design. There was an emphasis on using MRI measures to evaluate outcome. The study showed that with the numbers studied, useful data could be obtained on safety and on efficacy on certain MRI measures. A larger study would be required to evaluate treatment on disability in this patient cohort and further work is needed to elucidate the relationship between quantitative MR and clinical measures over the longer term.

Adjuvants, Immunologic↗

Cannabinoids inhibit neurodegeneration in models of multiple sclerosis.

Multiple sclerosis is increasingly being recognized as a neurodegenerative disease that is triggered by inflammatory attack of the CNS. As yet there is no satisfactory treatment. Using experimental allergic encephalo myelitis (EAE), an animal model of multiple sclerosis, we demonstrate that the cannabinoid system is neuroprotective during EAE. Mice deficient in the cannabinoid receptor CB1 tolerate inflammatory and excitotoxic insults poorly and develop substantial neurodegeneration following immune attack in EAE. In addition, exogenous CB1 agonists can provide significant neuroprotection from the consequences of inflammatory CNS disease in an experimental allergic uveitis model. Therefore, in addition to symptom management, cannabis may also slow the neurodegenerative processes that ultimately lead to chronic disability in multiple sclerosis and probably other diseases.

Animals↗

Interferon beta-1a in primary progressive multiple sclerosis.

There is currently no disease-modifying treatment proven to be of efficacy in primary progressive multiple sclerosis (PPMS). However, a number of therapeutic trials have recently been specifically designed for this group. These include a randomised controlled trial of interferon beta-1a which is discussed here. It is hoped that therapeutics in primary progressive multiple sclerosis will continue to expand and effective therapeutic agents will be developed.

Adjuvants, Immunologic↗

New T2 lesions enable an earlier diagnosis of multiple sclerosis in clinically isolated syndromes.

In clinically isolated syndromes, the new McDonald criteria for multiple sclerosis diagnosis require new gadolinium-enhancing lesions for dissemination in time at a 3-month follow-up magnetic resonance imaging scan. In a cohort of 56 patients, these criteria were specific (95%) but less sensitive (58%) for clinically definite multiple sclerosis at 3 years. If new T2 lesions were allowed as an alternative for dissemination in time, sensitivity increased (74%) with maintained specificity (92%), enabling an accurate diagnosis of multiple sclerosis in more patients.

Adolescent↗

Guidelines for using quantitative magnetization transfer magnetic resonance imaging for monitoring treatment of multiple sclerosis.

Quantitative evaluation of brain magnetic resonance imaging (MRI) scans is now an accepted part of the trial of new putative treatments for multiple sclerosis (MS). However, conventional MRI is not pathologically specific, and it does not reveal the details of the pathological processes that underlie the progression of the disease. Magnetization transfer (MT) imaging is a relatively new quantitative technique that appears to offer some pathological specificity, and can be used to monitor the changes over time in both individual lesions and the central nervous system as a whole. This paper considers the case for incorporating MT imaging into new clinical trials, so that the utility of MT for monitoring the modification of MS progression by treatment can be assessed. Specific guidelines for implementing MT imaging as part of a large multicenter clinical trial are given, and practical considerations when planning such a trial are detailed. It is anticipated that MT imaging will be incorporated into many new trials in the near future.

Brain↗

Application of a B-spline active surface technique to the measurement of cervical cord volume in multiple sclerosis from three-dimensional MR images.

PURPOSE: To evaluate the ability of a B-spline active surface technique to detect cervical spinal cord atrophy due to multiple sclerosis (MS) compared with intensity-based contouring. MATERIALS AND METHODS: In a previously reported study, the cervical spinal cords of 28 MS patients and 13 age-matched controls were imaged with a volume-acquired inversion-prepared fast spoiled gradient echo sequence at baseline and after one year. The images were reanalyzed using the B-spline technique and the results compared with the results obtained in the original report using intensity-based contouring. RESULTS: The mean cervical spinal cord volume determined by the active surface programme was 6487 mm(3) in 28 patients compared with 7117 mm(3) in controls (P = 0.002, corrected for age and gender). The patients' cervical spinal cord volumes were associated with expanded disability status scale scores (parameter estimate = -1.21 x 10(-3), r(2) = 0.39, P = 0.001). The patients' cervical spinal cord volumes did not decrease significantly over one year, unlike the mean cervical spinal cord areas at C2/3 calculated using intensity-based contouring. CONCLUSION: The active surface technique can detect cervical spinal cord atrophy due to MS, which has functional significance. However, this methodology is less sensitive at detecting small serial changes compared with the previously reported method.

Atrophy↗

Serum gelatinase B/MMP-9 in primary progressive multiple sclerosis patients treated with interferon-beta-1a.

BACKGROUND: Interferon- beta (IFNbeta) acts by a variety of mechanisms in relapsing-remitting multiple sclerosis (MS). One of these is a cellular down-regulation of gelatinase B or matrix metalloproteinase-9 (MMP-9), which is known from biochemical, biological and immunohistochemical evidences to play a disease-promoting role in MS. AIMS: a) To investigate the influence of IFNbeta-1a (30 or 60 micro g I. M./week) on serum MMP-9 levels in patients with primary progressive MS (PPMS). b) To correlate serum MMP-9 levels with clinical and magnetic resonance imaging (MRI) findings. METHODS: Serial blood samples were collected every 3 months from 49 patients participating in a phase II trial of IFNbeta-1a in PPMS. Serum MMP-9 was quantified by ELISA and correlations with clinical (EDSS) as well as MRI findings (brain and spinal cord atrophy, ventricular volume, T1 and T2 lesion load) were calculated. RESULTS: No significant differences were found between serial serum MMP-9 levels in IFNbeta-treated versus placebo-treated patients. MMP-9 levels did not differ between patients who progressed or did not progress during the study interval. Although mean absolute serum MMP-9 levels over the study period correlated with an increase in T2 lesion load (relative T2 change: r=0.51, p<0.001; absolute T2 change: r=0.30, p=0.038), absolute increase in brain ventricular volume (r=0.29, p=0.05) and increased brain atrophy (r=0.35, p=0.02), only the correlation with T2 lesion load was sustained throughout the study period. No correlations were found between MMP-9 levels and relative changes in ventricular volume or with relative/absolute changes in T1 lesion load and in spinal cord atrophy. None of the MRI measures correlated with MMP-9 changes between baseline levels and those on treatment. CONCLUSION: Although some evidence suggests a down-regulating effect of IFNbeta on MMP-9, this was not confirmed for a once weekly intramuscular dose of IFNbeta-1a in patients with PPMS. The sustained correlation between serum MMP-9 and changes in T2 volumes, and the lack of correlation with clinical or MRI measures of disease progression may suggest that MMP-9 is more directly related to non-specific central nervous system damage than to axonal loss.

Adult↗

Socio-demographic variables are limited predictors of health status in multiple sclerosis.

BACKGROUND AND OBJECTIVES: Self-reported health status measures reflect disease impact from the patient's perspective. However, such measures are not designed for individual patient use and are rarely used to guide clinical practice. Nevertheless, if strong predictors of health status can be demonstrated in large datasets, these could be used to identify people at risk of poor health states and help target interventions. The aim of this study was to examine the predictive value of routinely collected socio-demographic variables on health status. METHOD: Data for 638 patients with multiple sclerosis (MS) on the eight health dimensions of the Medical Outcomes Study 36-item Short Form Health Survey (SF-36) were collected either by a postal survey or hospital attendance and analysed by multiple regression analyses. RESULTS: Several sociodemographic variables, such as unemployment and manual social class had some predictive value on health status, but the effect was not strong (maximum cumulative variance explained 53 %). CONCLUSIONS: Sociodemographic variables that we studied were limited predictors of health status in MS and are of limited value in guiding clinical practice.

Adult↗

Does neurorehabilitation have a role in relapsing-remitting multiple sclerosis?

Patients with relapsing-remitting multiple sclerosis (RR MS) often make incomplete recovery from disabling exacerbations, despite corticosteroid treatment. Inpatient rehabilitation has been shown to be valuable in progressive MS, but its role in RR MS is less clear. We evaluated the effect of rehabilitation in consecutive patients with RR MS admitted to a neurological rehabilitation unit. Outcome measures applied on admission and discharge included the Expanded Disability Status Scale (EDSS), the Barthel Index (BI) and the Functional Independence Measure (FIM), as well as a visual analogue scale (VAS) of the patients' perception of rehabilitation impact. Confounding factors including the timing of steroid therapy and re-admissions were also examined. RR patients showed considerable improvement following rehabilitation, with a median change of -0.5 on EDSS, +4 on BI and +12 on FIM (mean change of -0.8 EDSS, +4.5 BI and +15.6 FIM points; effect sizes of -1.01, 0.97 and 0.86, respectively), which was significantly greater than other MS subtypes. RR patients rated their admissions highly (median VAS 8.9, interquartile range 7.5-9.9), and the VAS scores correlated modestly with disability measures (Spearman's rho = -0.42, 0.31 and 0.24 versus EDSS, BI and FIM, respectively; p = 0.007-0.040). Repeat admissions and the timing of steroid treatment did not have a significant effect on outcome. This suggests that inpatient rehabilitation is useful in RR MS, particularly in patients with incomplete recovery from relapses who have accumulated moderate to severe disability.

Adult↗

A study of the mechanisms of normal-appearing white matter damage in multiple sclerosis using diffusion tensor imaging--evidence of Wallerian degeneration.

Diffusion tensor imaging (DTI) investigates brain tissue microstructure in vivo. In multiple sclerosis (MS) Wallerian degeneration of axons traversing focal lesions is a potential mechanism of damage in normal-appearing white matter. In vivo evidence for this hypothesis is limited. The present study investigated the relationship between DTI-derived indices in the normal-appearing corpus callosum (CC) and the lesion loads (LLs) in connected cerebral regions. DTI was performed in 39 MS patients and in 21 age-matched controls. Fractional anisotropy (FA) and mean diffusivity (MD) were estimated in the genu, body and splenium of CC. Patients showed lower FA and higher MD in the CC than controls and both correlated with the total LL (r = -0.56 and r = 0.54, p < 0.0001). The LL of individual cerebral lobes correlated with both FA and MD in the corresponding callosal regions, with the body showing the strongest correlations with frontal and parietal LL (p < 0.0001). The strong correlations between DTI indices in the CC and the extent of lesions in connected brain regions support the hypothesis that Wallerian degeneration of axons transected by remote, but connected focal lesions, is an important pathogenic mechanism of damage in MS.

Adult↗

Effects of a short outpatient rehabilitation treatment on disability of multiple sclerosis patients--a randomised controlled trial.

It is well known that neurorehabilitation can reduce disability or improve handicap of people with multiple sclerosis (MS). The aim of this study was to evaluate the effectiveness of a short period (6 weeks) of a tailored, individualised outpatient rehabilitation program in people with progressive MS. A randomised-controlled trial was undertaken in patients with primary and secondary progressive MS referred to the Centro Sclerosi Multipla of Catania. One hundred and eleven patients were assessed at baseline and at 12 weeks with validated measures of disability (Functional Independence Measure (FIM)) and impairment (Expanded Disability Status Scale (EDSS) and Functional Systems Scale). Of the 111, 58 were randomly assigned to the treatment group and 53 to the control group. All patients had been previously trained in a home exercise program. Both groups were well matched for age, sex, disease duration and severity, disability and quality of life (Short Form-36). At the end of 6 weeks patients allocated to the rehabilitation treatment group showed significant improvement in their level of disability compared with the control group,while the level of impairment did not change. Thirty-two patients of the treatment group and four of the control group improved on the FIM by two or more steps at 12 weeks (p<0.0001). An improvement by 1 EDSS step occurred in only two patients of the treatment group and in one patient of the control group. Benefits were maintained for a further six weeks. This study demonstrates that a short outpatient rehabilitation treatment improves disability of MS patients, without changing their impairment and confirms the effectiveness of rehabilitation in people with MS.

Adult↗

The therapeutic potential of cannabis.

Research of the cannabinoid system has many similarities with that of the opioid system. In both instances, studies into drug-producing plants led to the discovery of an endogenous control system with a central role in neurobiology. Few compounds have had as much positive press from patients as those of the cannabinoid system. While these claims are investigated in disorders such as multiple sclerosis spasticity and pain, basic research is discovering interesting members of this family of compounds that have previously unknown qualities, the most notable of which is the capacity for neuroprotection. Large randomised clinical trials of the better known compounds are in progress. Even if the results of these studies are not as positive as many expect them to be, that we are only just beginning to appreciate the huge therapeutic potential of this family of compounds is clear.

Cannabinoids↗

A longitudinal study of abnormalities on MRI and disability from multiple sclerosis.

BACKGROUND: In patients with isolated syndromes that are clinically suggestive of multiple sclerosis, such as optic neuritis or brain-stem or spinal cord syndromes, the presence of lesions as determined by T2-weighted magnetic resonance imaging (MRI) of the brain increases the likelihood that multiple sclerosis will develop. We sought to determine the relation between early lesion volume, changes in volume, and long-term disability. METHODS: Seventy-one patients in a serial MRI study of patients with isolated syndromes were reassessed after a mean of 14.1 years. Disability was measured with the use of Kurtzke's Expanded Disability Status Scale (EDSS; possible range, 0 to 10, with a higher score indicating a greater degree of disability). RESULTS: Clinically definite multiple sclerosis developed in 44 of the 50 patients (88 percent) with abnormal results on MRI at presentation and in 4 of 21 patients (19 percent) with normal results on MRI. The median EDSS score at follow-up for those with multiple sclerosis was 3.25 (range, 0 to 10); 31 percent had an EDSS score of 6 or more (including three patients whose deaths were due to multiple sclerosis). The EDSS score at 14 years correlated moderately with lesion volume on MRI at 5 years (r=0.60) and with the increase in lesion volume over the first 5 years (r=0.61). CONCLUSIONS: In patients who first present with isolated syndromes suggestive of multiple sclerosis, the increases in the volume of the lesions seen on magnetic resonance imaging of the brain in the first five years correlate with the degree of long-term disability from multiple sclerosis. This relation is only moderate, so the volume of the lesions alone may not be an adequate basis for decisions about the use of disease-modifying treatment.

Adolescent↗

Application of the new McDonald criteria to patients with clinically isolated syndromes suggestive of multiple sclerosis.

Traditionally, multiple sclerosis (MS) has been diagnosed on the basis of clinical evidence of dissemination in time and space. Previously, it could not be diagnosed in patients with single clinical episodes of demyelination known as clinically isolated syndromes. New diagnostic criteria from the International Panel of McDonald and colleagues incorporate MRI evidence of dissemination in time and space to allow a diagnosis of MS in patients with clinically isolated syndromes. From clinical and MRI examinations performed prospectively at baseline, 3 months, 1 year, and 3 years of follow-up, the frequency of developing MS was ascertained by the application of both the new McDonald criteria and the Poser criteria for clinically definite MS. The specificity, sensitivity, positive and negative predictive value, and accuracy of the new criteria for the development of clinically definite MS were assessed. At 3 months, 20 of 95 (21%) patients had MS with the McDonald criteria, whereas only 7 of 95 (7%) had developed clinically definite MS. After 1 year, the corresponding figures were 38 of 79 (48%) and 16 of 79 (20%), and after 3 years, they were 29 of 50 (58%) and 19 of 50 (38%). The development of MS with the new MRI criteria after 1 year had a high sensitivity (83%), specificity (83%), positive predicative value (75%), negative predictive value (89%), and accuracy (83%) for clinically definite MS at 3 years. Use of the new McDonald criteria more than doubled the rate of diagnosis of MS within a year of presentation with a clinically isolated syndrome. The high specificity, positive predictive value, and accuracy of the new criteria for clinically definite MS support their clinical relevance.

Adolescent↗

The reproducibility and sensitivity of brain tissue volume measurements derived from an SPM-based segmentation methodology.

PURPOSE: To investigate the reproducibility of SPM99-based whole brain, gray matter, and white matter volume measurements with and without image inhomogeneity correction, subsequently exploring age and gender effects on absolute and fractional (proportional to intra-cranial) volumes. MATERIALS AND METHODS: Twenty-seven control subjects (aged 23.2 to 55.2 years) had three-dimensional fast spoiled gradient recall scans. Ten subjects were scanned about 197 days later. RESULTS: Coefficients of variation (CV) for absolute and fractional volumes determined from images processed with inhomogeneity correction ranged from 1.2% to 0.5%. Inhomogeneity correction reduced the CV for all measures except gray matter fractional (GMF) volumes. Significantly lower white matter absolute (WM) and fractional (WMF) volumes, and higher GMF were found in females compared with males, overlying age-related reductions (in decreasing order of significance) in brain parenchymal fraction, GMF, WMF, brain parenchymal, and gray matter volumes. CONCLUSION: SPM99 segmentations are sufficiently reproducible to detect age and gender effects in limited cohorts.

Adult↗