MS Abstracts 7b-2g1

Purpose
The aim of this study was to ascertain the health status and quality of life of a community based cohort of people with Multiple Sclerosis.

Method
A postal questionnaire with self-completed measures of Impairment, Disability, Physical Dependency and Quality Of Life was sent to a random sample of 203 people with Multiple Sclerosis from a population register.

The sample was stratified according to five disease courses. The population register is of the prevalent population of 760 people with Multiple Sclerosis resident in the Leeds Health Authority.

The register used multiple sources of ascertainment and is prospectively maintained with new incident cases.

Results
The estimated mean age of people with Multiple Sclerosis is 46 years (SE: 0.85), and mean duration of disease is 14.4 years (SE: 0.69). Almost four in five (78 %) are female, and one in six (17%) live alone.

Impairments of Balance, Vision and Memory are common and in all cases there is little difference in the frequency between disease course groups.

In contrast, Impairments of Bladder and Bowel are more common in those with a Progressive Disease course.

Disability is more common in those with a Progressive Disease course but all scores on the SF36 Physical Function scale are low and demonstrate the disabling consequences of the disease, irrespective of disease course.

These consequences must contribute to the fact that over two-thirds (68 %) were not employed at the time of the survey. Quality of life does not differ across disease course groups, but rather varies by age and duration.

Conclusions
People with Multiple Sclerosis experience a range of Impairments and Disabilities.

Those with Progressive Disease courses experience greater levels of Impairment and Disability than other groups. There is not a straightforward exchange between health status and quality of life.

A measure of subjective quality of life may reflect adjustment to disease, such that, for example, the longer the duration, the older the individual, the more likely the person will report a relatively good quality of life.

The pharmacological effect of GlucoCorticoids and Type 1 Interferons (IFNs), simultaneously used as therapeuticals for Multiple Sclerosis (MS), on the (inflamed) Blood-Brain Barrier (BBB) was investigated in vitro.

Although both drugs additively decreased BBB permeability, they did not prevent the increase in BBB permeability induced by LipoPolySaccharide (LPS), which served as a pro-inflammatory stimulus.

The beneficial clinical effect of GluCocorticoid and IFN therapy for MS seems there- fore not to be mediated through a direct action at the level of the BBB.

Most strikingly, however, pretreatment with Type 1 IFNs ( and ß) potentiated the effect of GlucoCorticoids by two orders of magnitude.

This lead us to hypothesize that Type 1 IFNs may restore the dysfunctional T-Helper 1 (Th1)/Th2 balance associated with MS, by a mechanism that involves an increased sensitivity for GlucoCorticoids.

Objective
The 36-item Short Form Health Survey Questionnaire (SF-36) is a widely used generic health status measure.

Recently it has been adapted to produce a disease-specific measure for MS-the 54-item Multiple Sclerosis Quality of Life Scale (MSQOL-54).

Composed of five unchanged SF-36 scales; three altered SF-36 scales (one item added to each scale); and five new scales incorporating 15 additional items.

This study evaluates the impact of these additions by comparing the measurement properties of the MSQOL-54 with the SF-36.

Methods
A total of 150 patients with MS, representing a broad spectrum of disease severity, completed a range of questionnaires, which included the MSQOL-54 (from which the SF-36 score was computed).

Of these, 44 people completed the measures before and after inpatient rehabilitation to evaluate responsiveness. Standard psychometric methods were used to evaluate the measurement properties.

Results
The measurement properties of the unchanged scales, inevitably, remain identical. Those of the three altered scales are virtually identical.

Of the five new scales, the validity of the two sexual scales is questioned because of the high percentage of missing data, and the validity of the overall quality-of-life scale is limited.

As demonstrated by the low to moderate correlations with other related and unrelated measures. Responsiveness of the new scales also appears limited.

Conclusion
Modifying existing measures by simply adding clinically chosen items may not be as useful as anticipated in improving the measurement properties of an instrument.

The aim of the present study was to verify the expression of Tumour Necrosis Factor-alpha (TNF-) mRNA by semiquantitative Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR).

In unstimulated peripheral blood MonoNuclear Cells (MNCs) of 15 Relapsing/Remitting Multiple Sclerosis (MS) patients who underwent treatment with IFN-ß-1a (6 millions of international units (MIU) i.m. once a week).

And in 15 untreated MS patients matched for age and Expanded Disability Status Score (EDSS).

At the same time the expression of TNF- mRNA was assessed in 10 healthy age-matched control subjects.

All MS patients were assessed at the basal time and after 6 months.

At the basal time, the band of TNF- mRNA was detectable in 12 out of the 15 untreated patients and in 13 out of the 15 patients who underwent IFN-ß-1a treatment.

The higher TNF- mRNA was evident in patients with Gadolinium-enhancing lesions.

At the 6-month follow-up, 13 out of the 15 untreated patients still had detectable values of TNF- mRNA and no significant difference emerged when compared with basal time.

On the contrary, the expression of TNF- mRNA was absent at the same time in nine out of the 15 patients treated with IFN-ß-1a.

A longitudinal analysis carried out monthly in eight MS patients (four untreated and four treated) revealed a transient increase in TNF- mRNA expression.

In MNCs of all four treated patients in the first 3 months, supporting previous findings of an early ImmunoEnhancing effect of IFN-ß-1a .

This early activation is followed by an inhibitory effect of IFN-ß-1a on TNF- mRNA expression in about 2/3 of treated MS patients when assessed at 6 months.

Further long-term studies are needed to confirm this ImmunoModulatory effect of IFN-ß-1a not only on TNF- but also on other Cytokines of Th1 and Th2 types.

Copyright 2001 Academic Press.

Inflammatory DeMyelinating Diseases comprise a heterogeneous group of disorders that affect the Peripheral and Central Nervous System. Multiple Sclerosis (MS) is the most common disease affecting the CNS White Matter.

Close similarities between MS and the animal model of the disease, Experimental Allergic Encephalitis (EAE), have suggested that MS might be an AutoImmune Disease, which is triggered by an infectious agent.

Our laboratory has directed its effort in identifying and designing therapies that interfere with key signaling pathways that mediate CNS inflammation in Experimental Allergic Encephalitis.

These have included naturally occurring Cytokines such as TGF-ß and synthetic small molecules, Lysofyline and Tyrphostin, which inhibit the inflammatory response and prevent the development of EAE.

Objectives
The objective was to correlate Magnetic Resonance Imaging (MRI) T₂-weighted lesion load and measures of White Matter Atrophy in the Brain to disability in a population-based sample of patients with Multiple Sclerosis (MS).

Material And Methods
A well defined cohort of patients was drawn at random from the general MS population by using the Danish Multiple Sclerosis Reigistry.

A semi-automated local thresholding technique was used to quantify T₂-weighted lesions on MRI; whereas manual tracing was applied to measure the Corpus Callosum Brain Ratio (CCR) and the Ventricle Brain Ratio (VBR).

Results
A sample of 86 patients with a mean age of 43.3 years (SD 4.3), mean disease duration of 13.6 years (SD 4.4) and a median Expanded Disability Status Score (EDSS) of 6.0 was identified.

The correlation between Total Lesion Area of the Brain (TLA) and Disability (EDSS) for the whole sample was moderate (Spearman rank correlation coefficient r=0.48, P<0.001).

Also correlations of CCR and VBR to Disability (r=0.32-0.46) were significant.

Conclusions
Correlations of TLA and disability in this study were rather strong.

Hence, T₂-weighted MRI lesion load in the Brain still plays an important role as a surrogate marker of disease and as a secondary outcome measure in Phase III treatment trials.

We investigated the incidence of Multiple Sclerosis (MS) in a Sicilian community located at sea level. The study was a retrospective search for MS patients.

Incidence was studied in the period from 1 January 1985 to 31 December 1994. We searched for Definite MS patients.

According to Poser's Criteria, among the population resident in Bagheria (Palermo province).

There were 25 subjects affected by MS, of which 20 were incident MS patients.

The average annual incidence was 4.4 per 100,000 persons (n = 453,385 person-years). The incidence increased over time (1985-1989 = 3.5, 1990-1994 = 5.3).

A parallel decrease of the interval between onset and diagnosis of MS was observed (1985-1989, 3.7 years, 95% CI = 1.6-7.3; 1990-1994, 1.9 years, 95% CI = 1.0-3.3). These results confirm that MS is frequent in Sicily.

Recent models of Experimental AutoImmune EncephaloMyelitis (EAE) have indicated that Antigens co-expressed in the Retina and Uvea might be of PathoGenetic relevance in Multiple Sclerosis (MS).

We investigated the clinical spectrum and Magnetic Resonance Imaging of 11 MS patients with concomitant Uveitis, and determined the frequency of clinically silent IntraOcular inflammation in a prospective series of 50 patients.

Two of the 11 patients had PanUveitis, seven had Anterior, and the remaining two had Intermediate Uveitis.

The onset of Uveitis preceded that of Neurological symptoms by a mean of 8.5 years (range 1-20).

None of the 50 MS patients studied prospectively by using Slit Lamp Examinations and Dilated Funduscopy showed any evidence of Uveitis but six patients had signs of Retinal inflammation ("Periphlebitis Retinae").

Cranial MRI did not reveal "atypical" lesional distribution in MS patients with Uveitis or Periphlebitis Retinae.

No correlation between the type of MS and Uveitis, or between the degree of Neurological disability and the type of Uveitis was found.

In Multiple Sclerosis (MS), HypoIntense lesions on T₁-weighted Magnetic Resonance Imaging are thought to represent areas of tissue disruption and Axonal loss.

In previous studies of MS patients, InfraTentorial T₁ HypoIntense lesions were found to be rare.

In MS patients selected to have chronic Cerebellar Ataxia, we have determined the extent of InfraTentorial T₁ HypoIntense lesions and their relationship with Disability.

We recruited nine patients with chronic Cerebellar Ataxia due to MS. An Expanded Disability Status Scale (EDSS) assessment was performed on each.

The patients' Brains were then imaged with Axial-oblique Dual-Echo Fast Spin-Echo and contrast-enhanced T₁-weighted conventional Spin-Echo sequences.

The number and total volume of InfraTentorial high-signal Lesions on T₂-weighted images and InfraTentorial HypoIntense lesions on T₁-weighted images were calculated by a blinded observer using a computer-assisted contouring technique.

A total of 96 InfraTentorial high-signal lesions were present, of which 62 (64.6%) appeared IsoIntense and 34 (35.4%) HypoIntense with respect to the surrounding Brain substance on the T₁-weighted images.

There was a median of 3 (range 0-10) and median volume of 0.43 ml (range 0-0.85 ml) InfraTentorial T₁ HypoIntense lesions per patient.

The EDSS score correlated with both the number (r=0.68, p=0.043) and the volume per patient (r=0.89, p=0.001) of InfraTentorial T₁ HypoIntense but not T₂ high-signal lesions.

InfraTentorial T₁ HypoIntense lesions are often seen in patients with MS and chronic Cerebellar Ataxia. They may play a significant role in the Disability suffered by these patients.

Background And Objective
Sexual dysfunction severely affects the quality of life of patients, but longitudinal studies of sexual function in Multiple Sclerosis are lacking.

We performed a study on a group of patients with Multiple Sclerosis to evaluate the change in sexual function and to examine the relationship between sexual dysfunction and other clinical variables over time.

Methods
A 2-year follow-up study on 99 patients with definite Multiple Sclerosis. Information on sexual and Sphincteric disturbances have been collected through face-to-face structured interviews.

Disability, independence, Cognitive performances and psychological functioning have also been assessed.

Spearman rank correlation analysis corrected for multiple comparisons, and linear regression analysis have been performed to test variables relationship and remove the effect of potential confounding covariates.

Results
The proportion of patients with sexual dysfunction remained over 70% and did not change during the 2-year follow-up, but the extent and number of symptoms increased significantly.

The number of symptoms of sexual dysfunction did not change significantly after an exacerbation. Significantly, more patients than before the study resorted to counseling and discussed with doctors of sexual matters.

In the univariate analysis, changes in sexual function over time correlated with changes in Bladder function (r=0.47, p<0.0001) and EDSS score (r=0.41, p<0.0001).

But the multivariate analysis demonstrated that only Bladder dysfunction was independently related to sexual dysfunction (R=0.36, p=0.003) when the effect of psychological factors were removed.

Conclusions
Symptoms of sexual dysfunction increase in significance and number over time in patients with Multiple Sclerosis.

Relapses did not influence the number of symptoms of sexual dysfunction, but a worsening of pre-existing symptoms cannot be excluded.

The change of sexual function appears to be independently associated to Bladder dysfunction.

During retrospective and prospective studies, we attempted to determine the clinical characteristics, treatment, and Visual outcome of patients with Pars Planitis.

And to evaluate the association between Pars Planitis and Multiple Sclerosis (MS).

The retrospective study included 44 patients with Pars Planitis, who had been examined between October 1986 and January 1999.

We analyzed age, sex, Visual Acuity (VA), median follow-up time, and medical and surgical treatments.

The prospective study, which included 21 consecutive patients with Pars Planitis, was performed to determine the presence of MS. In the retrospective study, the mean patient age was 22.4 years (SD +/- 11.5) and the median follow-up was 34.9 months (SD +/- 27.2).

Complications included Macular Edema (47.7%), Vitreous Opacities (38.6%), Papillitis (38.6%), Vasculitis (36.4%), and Cataract (20.5%). Forty patients (90.9%) had a final bilateral VA better than 20/40.

In the prospective study, Magnetic Resonance Imaging (MRI) was performed. DeMyelinating lesions were found in 10 (47.6%) of the 21 patients and Relapsing/Remitting Clinically Definite MS was diagnosed in seven (33.3%).

With the exception of age, no significantly statistical differences were observed.

When the Visual prognosis and the clinical and Epidemiologic characteristics were compared between the two groups of patients with and without associated MS.

A diagnosis of MS was more frequently made in patients over 25 years of age. With appropriate treatment, patients with Pars Planitis have a good Visual prognosis.

Because the presence of DeMyelinating Lesions seems to be high among patients with Pars Planitis, MRI should be considered, especially in patients over 25 years of age.