MS Abstracts: 2b-2g

OligoClonal Bands (OCBs) are frequently observed in the CerebroSpinal Fluid (CSF) of patients with Multiple Sclerosis (MS), but the target Antigens of these AntiBodies remain unknown.

We used Antigen specific ImmunoBlotting to determine whether Epstein Barr Virus Nuclear Antigen-1 (EBNA-1) was a target of the OCBs in the CSF of patients with MS.

AntiBody indices (AIs) were measured by ELISA and calculated by the formula of Reiber and Lange which includes correction factors for both breakdown of the Blood-Brain Barrier and Intrathecal PolyClonal IgG synthesis.

A distinctive OligoClonal Antigen specific banding pattern for EBNA-1 was observed in 5/15 MS patients, but 0/12 controls (P=0.037, Fisher's Exact Probability).

AIs in this EBNA-l positive subgroup were extremely high, comparable with levels observed in Viral CNS infections.

In one patient with EBNA-1 specific OCBs, EBNA-1 and a peptide 'equivalent', p62, were able to absorb a component of the total IgG. Our results suggest that in a subset of MS patients, EBNA-1 may be a major target of selected OCBs.

We investigated the effect of Oral and IntraVenous MethylPrednisolone treatment on subsequent relapse rate in patients with Multiple Sclerosis.

Following a double blind trial designed to compare the effect of Oral and IntraVenous MethylPrednisolone treatment on promoting recovery from acute relapses of Multiple Sclerosis, 80 patients were followed for two years with six-monthly assessments during which all subsequent relapses were recorded.

The annual relapse rate was slightly higher in the Oral compared with the IntraVenous MethylPrednisolone-treated patients (1.06 vs. 0.78), but the adjusted difference between the two groups was not statistically significant (0.18; 95% CI -0.19 to 0.55, P=0.3).

The time to onset and the severity of the first relapse after treatment, the number of relapse free patients at the end of the follow-up period, and the severity of the relapses during the follow-up period were similar in the two groups.

This trial did not show a statistically significant difference in relapse rate during the first two years following Oral compared with IntraVenous MethylPrednisolone treatment.

In Multiple Sclerosis patients, Magnetic Resonance Imaging (MRI) frequently detects lesions in the BrainStem and Cerebellum.

However various pathologies that have a predelection to occur in Posterior Fossa Parenchyma may share similar features with Inflammatory-DeMyelinating lesions. In this paper, we review the contribution of MRI to the differential diagnosis of Posterior Fossa pathology.

Vascular lesions due to Chronic Hypoperfusion and ArterioloSclerosis or Occlusion of the main supplying arteries of the posterior circulation leading to Acute Infarction frequently produce characteristic Pontine or Cerebellar lesions.

Neoplastic Disease, in particular Pontine Gliomas in younger patients may have similar MRI features and may be difficult to distinguish from Inflammatory-DeMyelinating lesions.

Central Pontine Myelinolysis usually occurs in severely ill patients but the Pontine MRI changes have an overlapping profile with Inflammatory DeMyelination.

Diffuse Axonal injury of the MidBrain and BrainStem after head trauma and Atrophy of Posterior Fossa structures in Degenerative Diseases may appear similar on MRI to tissue changes also seen frequently in MS.

Analysis of the MRI appearance and clinical information is most often useful to narrow the fairly long list of differential diagnoses of Posterior Fossa pathology.

Examination of the Posterior Fossa by Magnetic Resonance Imaging is discussed with respect to modern techniques and equipment, and including recent results of non-conventional studies in Multiple Sclerosis.

Optimal protocol design will maximize resolution and signal strength while providing diagnostic contrast. Motion artifact from the Sigmoid and Transverse Sinuses may appear as ghosting and can be mitigated with proper imaging parameter choices.

Imaging considerations for the diagnosis and differential diagnosis of MS are based primarily on results of MR studies of the Brain.

Recent studies suggest that with current technology, MR imaging of the Spinal Cord can make important contributions, particularly in cases with equivocal or negative Brain MRI studies. Spinal Cord MRI may also assume an important role in early diagnosis.

The MR imaging-based assessment of the Optic Nerve in Optic Neuritisand Multiple Sclerosis provides information that is complementary to clinical and electrophysiological methods.

The standard and more tissue destruction specific methods can be used in strategies to measure treatment efficacy and for understanding the mechanisms of relapse, recovery, and failure of recovery.

Although the correlations between Magnetic Resonance Imaging (MRI) findings and long-term disease evolution range from poor to moderate, conventional pre- and post-contrast MRI provides sensitive and reliable measures to monitor Multiple Sclerosis (MS) activity over time.

MRI pulse sequences that have been recently introduced have shorter acquisition times and their use in large-scale studies can significantly decrease their costs in terms of both working load and patients' discomfort.

The application of non-conventional techniques can increase the pathological specificity of MRI findings and, as a consequence, improve the relationship with the clinical evolution of the disease.

These techniques also enable us to quantify the subtle abnormalities occuring in the so-called Normal-Appearing White Matter, thus allowing a more accurate assessment of MS burden to be achieved.

Some of these techniques have already shown their value for assessing MS dynamics, whereas other still need to go through a more complete validation process prior to any extensive clinical application in MS.

In Multiple Sclerosis (MS), induction of T-Cell Apoptosis constitutes a promising therapeutic strategy.

Recently, Bisindolylmaleimide has been shown to be an effective treatment of Experimental AutoImmune EncephaloMyelitis, presumably due to enhancement of CD95-mediated T-Cell Apoptosis.

Therefore, we studied the effects of Bisindolylmaleimide on human (auto)Antigen-specific T-Cells.

We observed a synergistic effect of Bisindolylmaleimide with Apoptotic stimulus assessed via caspase activity and annexin V-binding, but no potentiation of DNA fragmentation or cell death.

Thus, Bisindolylmaleimide might be useful for modulating T-Cell Apoptosis, yet more potent substances have to be generated re-establishing Immunological control over auto-reactive T-Cells.

The effect of Apoptosis inhibitors on Experimental AutoImmune EncephaloMyelitis (EAE), a model for Multiple Sclerosis, was investigated by intraperitoneal or intracisternal administration of Apoptosis inhibitors Ac-YVAD-cmk and zVAD-fmk.

After onset of the disease, these agents had no suppressive effect on EAE and resulted in impaired recovery or earlier relapse.

Histological examination revealed that administration of zVAD-fmk suppressed the Apoptotic death of Inflammatory cells in the Central Nervous System (CNS) of mice with EAE.

The results indicated that the Apoptotic elimination of infiltrated cells in the CNS might be one of the recovery mechanisms in EAE.

Copyright 2000 Academic Press.

Objectives
Understanding the properties of an outcome measure is essential in choosing the appropriate instrument and interpreting the information it generates.

The MOS 36 item short form health survey questionnaire (SF-36) is widely acknowledged as the gold standard generic measure of health status; few studies however have evaluated its use for clinical trials in Multiple Sclerosis.

Its clinical appropriateness, internal consistency reliability, validity, and responsiveness was investigated across a broad range of patients with Multiple Sclerosis.

Methods
A prospective study in which 150 adults with clinically definite Multiple Sclerosis completed a battery of questionnaires evaluating generic health status, disability, handicap, and emotional wellbeing.

Of these, 44 patients undergoing inpatient rehabilitation completed the questionnaires before and after intervention to evaluate responsiveness.

Results
Score distributions demonstrated significant floor and ceiling effects in four of the eight dimensions which were particularly marked when patient selection was restricted to a narrow band of disease severity (as is the case in most clinical trials).

Internal consistency exceeded the standard for group comparisons for all dimensions. Convergent and discriminant construct validity was supported by the direction, magnitude, and pattern of correlations with other health measures.

In comparison with instruments measuring associated constructs, the responsiveness of the SF-36 was poor in evaluating change in moderate to severely disabled patients participating in a programme of inpatient rehabilitation.

Conclusions
The SF-36 has some limitations as an outcome measure in Multiple Sclerosis.

The results highlight the need for all instruments to be examined in the specific sample population under question and for the specific research question being investigated.