Multiple Sclerosis - Abstracts 9-99

Scores on the Univ of Pennsylvania Smell Identification Test (UPSIT), as well as the numbers of MRI-determined plaques within the inferior Frontal and Temporal Lobes, were obtained on three or four separate occasions in each of five MS patients over an 18- to 20-month period.

A close association was observed, longitudinally, between the remission and exacerbation of plaque numbers and UPSIT scores, with more plaques reflecting lower UPSIT scores.

These observations further support the hypothesis that Olfactory loss in MS is associated with fluctuations in Plaque numbers in central Olfactory Brain regions.

The authors describe five patients with Trochlear Nerve Palsy and MS to characterize this rare association. In two patients, Trochlear Nerve Palsy was the initial clinical manifestation of MS.

In the other three patients, this sign occurred after previous Neurologic events. MRI did not identify a lesion of the Fourth Nerve Nucleus or Fascicle. Ophthalmoplegia resolved within 2 months in four of the five patients.

A reason this association is rare is that the fascicular course of the Trochlear Nerve is exposed to little Myelin.

We compared the number of new Gadolinium-enhancing and T₂-weighted lesions on six monthly MRI scans in eight patients with Relapsing Multiple Sclerosis.

Before and during treatment with weekly intramuscular Interferon-ß-1a (Avonex; 30 microg), MRI activity was modestly reduced during treatment (p = 0.016).

The treatment effect was also significant after adjusting pretreatment lesion frequency for regression to the mean. Based on this pilot study, Avonex, as approved for treatment of Relapsing forms of MS in the United States, reduces new MRI activity.

Objective
To use the new consensus definitions of Primary/Progressive Multiple Sclerosis (PPMS) and Progressive/Relapsing Multiple Sclerosis (PRMS) to report the demographic, clinical, and natural history characteristics of Multiple Sclerosis (MS) that is Progressive from the time of onset.

Design & Setting
Retrospective study by database/chart review and telephone interview. Multiple Sclerosis clinic at a university teaching hospital.

Patients
Eighty-three patients (prevalence, 6.9%) with PPMS and 12 patients (prevalence, 1.0%) with PRMS were studied.

Results
Fifty-nine percent of the patients with PPMS (n=49) and 67% of the patients with PRMS (n=8) were women. Mean +/- SD ages at the time of onset were 41.2 +/- 10.5 and 38.0 +/- 7.3 years, respectively; mean disease duration was 14.2 +/- 8.8 and 12.2 +/- 6.5 years, respectively.

The initial symptoms involved Leg Weakness in 94% of the patients with PPMS (n = 78) and 100% of the patients with PRMS (n= 12).

For the PPMS cohort, a syndrome consistent with isolated Myelopathy was found in 36% of patients (n = 30) and Arm Weakness without Leg Weakness did not occur.

Mean +/- SEM time of progression to a score of 6.0 on the Expanded Disability Status Scale was 10.2 +/- 1.0 years for patients with PPMS and 10.9 +/- 2.6 years for patients with PRMS.

Conclusions
The clinical characteristics and Disability progression of these MS subtypes were indistinguishable, with the exception of 1 or 2 relapses in patients with PRMS that occurred 8 months to 9 years after the onset of symptoms.

We see little reason to consider PPMS and PRMS separate clinical entities; however, whether they can be better distinguished by Radiological, HistoPathological, or Immunological markers of disease activity remains unknown.

With the development of effective therapies for Multiple Sclerosis (MS), therapeutic nihilism, which was so prevalent just 10 years ago, has given way to exuberance and optimism. The current mood is understandable because MS is such a devastating disease.

Within 10 years of symptom onset, 50% of patients with MS are unable to carry out household and employment responsibilities; within 15 to 20 years, 50% are unable to walk unassisted; and within 25 years, 50% are unable to walk at all.

The average annual cost of MS in the United States has been estimated at greater than $6.8 billion, or $34 103 per person.

This review summarizes evidence that disease-modifying drugs can significantly improve the course of patients with Relapsing/Remitting MS (RRMS) and frames key issues relating to the use of current drugs. Major issues confronting experimental MS therapeutics are discussed.

Context
The greatest needs of people with chronic conditions are long-term care, maximized independence, and improved quality of life.

With conventional medicine becoming increasingly expensive, depersonalized, and unable to adequately meet such needs, many with chronic conditions are seeking health promotion strategies to effectively manage their symptoms.

Objective & Design
An 8-week t'ai chi program was conducted to explore psychosocial and physical benefits for those with Multiple Sclerosis. Nonrandomized, noncontrolled pilot study.

Setting & Patients & Intervention
American College of Traditional Chinese Medicine, San Francisco, Calif. 19 patients with Multiple Sclerosis. Doing T'ai chi.

Main Outcome Measures
Walking Speed (distance = 25 ft), Hamstring Flexibility, and Psychosocial well-being as measured by the Medical Outcomes Study 36-item Short-form Health Survey.

Results
Walking Speed increased by 21% and Hamstring Flexibility increased by 28%. Patients experienced improvements in vitality, social functioning, mental health, and ability to carry out physical and emotional roles.

Conclusions
This pilot program was conducted entirely on a volunteer basis and led to the implementation of several additional T'ai Chi classes for people with Multiple Sclerosis across the United States.

T'ai Chi and other health promotion programs offer help toward achieving the goals of increasing access to services, maximizing independence, and improving quality of life for people with chronic disabling conditions.

The elective treatment of patients with Multiple Sclerosis, using a humanized Anti-Leukocyte (CD52) MonoClonal AntiBody (Campath-1H), has illuminated mechanisms that underlie the clinical course of the disease.

Twenty-seven patients were studied clinically and by Magnetic Resonance Imaging (MRI) before and for 18 months after a single pulse of Campath-1H.

1. The first dose of MonoClonal AntiBody was associated with a transient rehearsal of previous symptoms caused by the release of mediators that impede Conduction at previously DeMyelinated sites
   • This effect remained despite selective blockade of Tumor Necrosis Factor-

2. Disease activity persisted for several weeks after treatment but thereafter Radiological markers of Cerebral Inflammation were suppressed for at least 18 months during which there were no new symptoms or signs

3. However, about half the patients experienced Progressive Disability and increasing Brain Atrophy, attributable on the basis of MRI Spectroscopy to Axonal Degeneration
   • Which correlated with the extent of Cerebral inflammation in the pretreatment phase

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These data support the formulation that Inflammation and DeMyelination are responsible for relapses of Multiple Sclerosis

1. Inflammatory mediators, but not Tumor Necrosis Factor-, cause symptomatic reactivation of previously DeMyelinated lesions
2. Axonal Degeneration, conditioned by prior Inflammation but proceeding despite its suppression, contributes to the Progressive phase of Disability

These results provide evidence supporting the emerging view that treatment in Multiple Sclerosis must be given early in the course, before the consequences of inflammation are irretrievably established.

Myelin Basic Protein (MBP)-reactive T-Cells may play an important role in the AutoImmune PathoGenesis of Multiple Sclerosis (MS).

MBP-reactive T-Cells can be specifically targeted by T-Cell vaccination, a procedure whereby MS patients are immunized with attenuated autologous MBP reactive T-Cells. T-Cell vaccination induces Immune Responses to the vaccine cells together with a depletion of MBP reactive T-Cells.

Forty-nine MS patients were treated with T-Cell vaccination in an extended phase I trial to study the safety, Immune Responses and clinical effects of T-Cell vaccination.

In the present paper the Immune Responses towards the vaccine cells were characterized. Substantial long-term in vitro proliferative responses were observed in all treated patients.

Some patients, immunized with different clones, displayed distinct proliferative reactivity against the various vaccine clones, suggesting unequal Immunogenic properties of these clones.

Reactive TCRalphaB⁺, CD8⁺ and CD4⁺T-Cells, and to a lesser extent, d T-Cells and NK Cells were observed to in vitro stimulation with the vaccine cells.

A small fraction only of CD8⁺T-Cells expressed CytoLytic and inhibitory anti-clonotypic reactivity against the vaccine cells.

Stimulation with the vaccine clones predominantly induced expression of ProInflammatory Cytokines in these mixed cultures, although one vaccine clone consistently induced production of IL-4.

CD4⁺T-Cells are the major Cytokine-producing cells in these anti-vaccine lines. We could not detect upregulated AntiBody responses to the vaccine cells in most patients, although a temporary AntiBody response was observed in one patient.

In conclusion, immunization with attenuated AutoReactive T-Cells induces a complex Cellular Response specifically targeted at the vaccine cells, but no AntiBody responses.

These data provide further insights into the mechanisms of T-Cell vaccination and improve our understanding of the complex regulatory networks of AutoReactive T-Cells.

Copyright 1999 Academic Press.