We compared the sensitivity of single and triple dose Gd-DTPA Magnetic Resonance Imaging (MRI) in detecting enhancing lesions in the Spinal Cord (SC) from 15 patients with Multiple Sclerosis (MS).

The patients were examined monthly on four occasions. We detected two enhancing lesions in two of 15 (13%) patients when a single dose of Gd-DTPA was used.

No additional lesions were detected when a triple dose of Gd-DTPA was used. These results confirm:

1. That enhanced Spinal Cord imaging does not significantly increase the detection of active lesions in MS

2. They do not support the general application of triple dose Gd-DTPA when examining the SC

3. Suggest that further studies taking into account SC symptoms are necessary

Multiple Sclerosis (MS) is an Immune-mediated disease that may be amenable to high-dose ImmunoSuppression with peripheral blood Stem Cell Transplantation (SCT) in selected patients.

Five MS patients (all women, ages 39-47 years) received Granulocyte Colony-Stimulating Factor (G-CSF) for Stem Cell mobilization, CD34 cell selection for T-Cell depletion, a preparatory regimen of Busulfan (1 mg/kg x 16 doses) and Cyclophosphamide (120 mg/kg), and Antithymocyte Globulin (10 mg/kg x 3 doses) at the time of Stem Cell infusion.

Days required to recover absolute Neutrophil count >500 were 12 to 14 and platelet count >20,000 were 17 to 58.

PostTransplantation infectious complications in the first year after SCT occurred in 3 of 5 patients, and 1 patient died at day 22 after SCT from Influenza A Pneumonia.

Neuropathologic study in this patient showed DeMyelinating plaques with surrounding Macrophages but only rare T-Cells. In 2 patients, MS flared transiently with G-CSF.

Magnetic Resonance Imaging Gadolinium enhancement was present in 3 of 5 patients before transplantation and 0 of 4 after SCT.

There were CerebroSpinal Fluid Oligoclonal Bands at 1 year after SCT, similar to the pretransplantation assays.

Sustained suppression of Peripheral Blood MonoNuclear Cell proliferative responses to Myelin antigens occurred after SCT, but new responses to some Myelin peptide fragments also developed after SCT.

In 1 patient, enzyme-linked immunospot (ELISPOT) assays done 9 months after SCT showed a predominant T-helper 2 (Th2) Cytokine pattern.

Neurological progression of 1 point on the Extended Disability Status Scale was seen in 1 patient 17 months after SCT.

Another patient who was Neurologically stable died abruptly 19 months after SCT from overwhelming S. pneumoniae sepsis.

The remaining patients have had stable MS (follow-up, 18 and 30 months). In summary, our experience confirms the high-risk nature of this approach.

Further studies and longer follow-up would be needed to determine the significance of new Lymphocyte proliferative responses after SCT and the overall effect of this treatment on the natural history of MS.

Objectives
To obtain a simple and reliable clinical parameter for the diagnosis of Multiple Sclerosis among patients with Neurological Diseases.

Patients And Methods
Heparinized peripheral blood was obtained from patients with Multiple Sclerosis and those with Non-Inflammatory Neurological Diseases and healthy volunteers.

A new enzyme immunoassay method determining medullasin levels in human Granulocytes was developed by using mouse MonoClonal Antibody against medullasin.

Results
A newly developed Enzyme ImmunoAssay method for medullasin can detect as little as 1 ng/ml medullasin and results can be obtained within 2 h.

Eighty-five out of 112 patients with Multiple Sclerosis (75.8%) showed positive results (above means of normals + 2 SD) in the medullasin test, while 15.4% (12/78) of patients with non-inflammatory Neurological Disease had positive results.

Conclusion
This newly developed Enzyme ImmunoAssay method for medullasin is considered to be a useful paraclinical test for the diagnosis of Multiple Sclerosis.

Objective
A protocol system is being used in Spain for the prescription of innovative drugs including Interferon beta-1b (IFN-ß-1b).

Petitions for dispensing and reimbursement are based on the inclusion and exclusion criteria of pivotal trials, and are reviewed individually for approval by specialist committees.

To estimate the performance of IFN-ß-1b in the clinical setting, data collected by the INSALUD and regional health services of Andalusia and Catalonia, together responsible for the healthcare of nearly 30 million individuals, were compiled in a common database for analysis.

Methods
Data comprise demographic and disease characteristics at the time of petition and at follow-up 3 months after treatment initiation and every 6 months thereafter.

Efficacy was estimated by mean number of relapses per year, proportion of relapse-free patients, and disease progression as measured by the Expanded Disability Status Scale (EDSS).

Safety parameters included adverse events and laboratory analyzes.

Results
Between September 1995 and database cutoff in mid-1998, petitions of 1419 patients were approved for IFN-ß-1b treatment.

Patients were homogenous across the three databases and in the subgroups of patients completing 1 year (n = 940) and 2 years (n = 302) of treatment.

There was a marked decrease in the mean number of relapses in the first 12 months of IFN-ß -1b treatment for the 938 patients documented for 12 months, with a mean of 0.4 (+/- 0.7 SD) relapses per patient and year, and a 2-year mean of 0.9 (+/- 1.20 SD) in the 302 patients documented for 24 months.

Of the 938 patients followed for > or = 12 months, 505 (53.8%) were documented as being relapse-free during 12 months of treatment, and 146 (48.3%) of the 302 patients followed for > or = 24 months, were relapse-free during 24 months of treatment.

There were no differences in mean or median EDSS scores between baseline and months 12 and 24.

Skin disorders were the most frequent adverse events, reported in over one-third of all patients; there were 159 injection site events, most frequently Erythema (115 events).

Systemic AEs pointing towards flu-like symptoms were reported in 288 of 1419 patients (20.3%). Leukopenia was the most frequently reported laboratory event.

Elevations in Liver transaminases were noted for 12 patients (0.8%) with SGOT increase and 7 (0.5%) with SGPT increase.

Conclusion
The protocol system has helped make IFN treatment available to 8-10% of the estimated 15,000-18,000 MS patients in the regions studied. In terms of efficacy, IFN-ß-1b performed in line with the pivotal study results.

The safety profile of IFN-ß-1b was consistent with the published findings and the drug labelling, and no new side effects or increased incidence of known side effects was observed.

Aim
To provide information about the diagnostic and therapeutic impact of Magnetic Resonance Imaging (MRI) and to compare the findings across diagnostic groups.

Materials And Methods
A prospective, observational study of 2017 consecutive referrals for MRI of the Head, Spine or Knee at four imaging centers.

Clinicians completed questionnaires before MRI stating initial diagnoses, diagnostic confidence and treatment plans.

After imaging, a second questionnaire evaluated clinicians' revised diagnosis and treatment plans in the light of imaging findings.

Patients were grouped into nine diagnostic categories for analysis. Comparison between pre- and post-imaging was used to assess the diagnostic and therapeutic impact of MRI.

Results
In seven of nine diagnostic groups MRI findings were associated with a diagnostic impact. Diagnoses were revised or discarded following normal MR findings and diagnostic confidence was increased by confirmative MR findings.

There was no statistically significant diagnostic impact for suspected Pituitary or Cerebello-Pontine Angle lesions.

In five of nine diagnostic groups (Knee Meniscus, Knee Ligament, Multiple Sclerosis, Lumbar and Cervical Spine) MRI findings had a clear impact on treatment plans.

Conclusion
This study demonstrates that in most diagnostic categories, MRI influences diagnosis and treatment. However, experimental studies are needed to prove that these diagnostic and therapeutic impacts lead to improved health.

Copyright 2000 The Royal College of Radiologists.

This study was conducted to further establish the significance of the previously reported association between Depressive Symptoms and DeMyelinating lesions in the region of the Left Arcuate Fasciculus in Multiple Sclerosis patients.

The Beck Depression Inventory (BDI) was broken down into its main symptom categories on the basis of well-established factor analyzes from the literature, and the correlation pattern between the resulting BDI subscores and lesion measurements was analyzed.

We found that lesions of the Left Arcuate Fasciculus region were selectively associated with BDI items expressing patients' Affective Symptoms and Somatic Complaints.

Specifically, lesion measurements from this Brain location accounted for 26% of symptom score variance of the BDI part that includes only these two factors.

Performance Difficulties and Cognitive Distortions were not consistently associated with the lesion measurement.

Performance Difficulties, however, showed a high correlation with the Neurologic deficit detected in the physical examination.

These results show that lesions in the Left Arcuate Fasciculus region are associated with the core of the Depressive Syndrome rather than marginal symptoms and, thus, further suggest that this Left SupraInsular Brain region involves White Matter tracts relevant to Mood Regulation.

Kurtzke's EDSS remains the most widely-used measure for clinical evaluation of MS patients. However, several studies have demonstrated the limited reliability of this tool.

We introduce a computerized instrument, MS-CANE (Multiple Sclerosis Computer-Aided Neurological Examination), for clinical evaluation and follow up of patients with Multiple Sclerosis (MS) and to compare its reliability to that of conventional Expanded Disability Status Scale (EDSS) assessment.

We developed a computerized interactive instrument, based on the following principles: structured gathering of neurological findings, reduction of compound notions to their basic components, use of precise definitions, priority setting and automated calculations of EDSS and Functional Systems scores.

An expert panel examined the consistency of MS-CANE with Kurtzke's specifications.

To determine the effect of MS-CANE on the reliability of EDSS assessment, 56 MS patients underwent paired conventional EDSS and MS-CANE-based evaluations.

The inter-observer agreement in both methods was determined and compared using the kappa statistic. The expert panel judged the tool to be compatible with the basic concepts of Kurtzke's EDSS.

The use of MS-CANE increased the reliability of EDSS assessment: Kappa statistic was found to be 0.42 (i.e. moderate agreement) for conventional EDSS assessment versus 0.69 (i.e. substantial agreement) for MS-CANE (P=0. 002).

We conclude that the use of this tool may contribute towards a standardized and reliable assessment of EDSS.

Within clinical trials, this could increase the power to detect effects, thus reducing trial duration and the cohort size required.

Multiple Sclerosis (2000) 6 355 - 361

The aims of this study were to investigate (i) the self-reported frequency and intensity of systemic side-effects and their impact on the daily lives of patients suffering from Multiple Sclerosis (MS) and undergoing Interferon-ß therapy and (ii) the self-reported frequency and perceptions of any local-tissue reactions.

Forty patients aged 22 - 59 years (27 females) with Relapsing/Remitting MS were consecutively recruited for the study (17 on interferon-beta-1a and 23 on Interferon-beta-1b).

Two self-administered questionnaires were used before and after 1, 4, 8 and 16 weeks of therapy.

The Interferon therapy was found to be associated with flu-like symptoms. Most systemic side-effects were reported to be mild and to have little impact on the patients' daily lives.

Asthenia and Fatigue were more often rated as moderate or severe.

The most frequently reported local-tissue side-effects were redness and local pain at the injection sites.

A considerable inter-individual variation was found among patients regarding the perceptions of both the systemic and local side-effects.

This suggests that it is of importance to identify early those patients who may need more support or other interventions to maintain a successful compliance.

Multiple Sclerosis (2000) 6 349 - 354

Multiple Sclerosis [MS], a DeMyelinating disease of the Central Nervous System associated with inflammation and Gliosis, may be an AutoImmune Disease with T-Lymphocytes and AutoAntibodies to Myelin protein(s).

This study deals exclusively with B-Cell AutoImmunity to Myelin Basic Protein (MBP).

T-Lymphocytes and Anti-MBP share a common MBP Epitope located between P85 and P96 which contains the essential contact residues H88FFK91 for the trimolecular complex.

The purpose of this Phase I open label clinical study was to monitor CSF Anti-MBP in patients with Chronic/Progressive MS subsequent to IV administration of Synthetic Peptide (SP) MBP82-98 namely Den85vvhffknivtp96rt.

Fifty-six patients who participated in this project were assigned to two groups: a 'control group' of 15 patients who received IV saline injections every 6 months for the first 2 years of the study.

And a 'Peptide Group' of 41 patients who received IV spMBP82-98 from the beginning of the study and then infrequently subsequent to a rise of their CSF Anti-MBP.

In the control group AntiBody levels remained persistently elevated during the 2 year period.

Patients in the 'peptide group' segregated into four kinetic profiles:
1. Cohort A (15 patients) illustrated prolonged Anti-BMP suppression into the normal range
2. Cohort B (10 patients) illustrated significant Anti-MBP suppression into the normal range for shorter durations
3. Cohort C (eight patients) showed significant CSF Anti-MBP suppression after the initial injection but lost the ability to suppress the AutoAntibody titer following subsequent injections
4. Cohort D (eight patients) failed to show significant CSF Anti-MBP suppression.

In conclusion the B-Cell tolerizing effect of SPMBP82-98 segregated into four kinetic profiles.

This molecular variability should be considered in attempts to develop specific 'peptide therapies', for the broad range of clinical profiles currently diagnosed as 'Multiple Sclerosis'.

Multiple Sclerosis (2000) 6 300 - 311