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MS - Abstracts 11d-2g

  1. Fatigue and declines in Cognitive functioning in Multiple Sclerosis
    Neurology 2000 Oct 10;55(7):934-9

  2. Cortical Evoked Potentials of the Dorsal Nerve of the Clitoris and female Sexual Dysfunction in Multiple Sclerosis
    J Urol 2000 Dec;164(6):2010-2013

  3. Significant correlation between IL-10 levels and IgG indices in Multiple Sclerosis CerebroSpinal Fluid
    J NeuroImmunol 2000 Nov 1;111(1-2):64-67

  4. Female sex steroids: effects upon Microglial cell activation
    J NeuroImmunol 2000 Nov 1;111(1-2):77-85

  5. Interferon-ß treatment in Multiple Sclerosis decreases the number of circulating T-Cells producing Interferon-gamma and InterLeukin-4
    J NeuroImmunol 2000 Nov 1;111(1-2):86-92

  6. VLA-4/CD49d downregulated on primed T-Lymphocytes during Interferon-ß therapy in Multiple Sclerosis
    J NeuroImmunol 2000 Nov 1;111(1-2):186-194

  7. CD4+ CD45RO+)CD49d (high) cells are involved in the PathoGenesis of Relapsing/Remitting Multiple Sclerosis
    J NeuroImmunol 2000 Nov 1;111(1-2):215-223

  8. Pattern of Cytokine secretion by peripheral blood cells of patients with Multiple Sclerosis in Brazil
    Mult Scler 2000 Oct;6(5):293-9

  9. Importance of paraclinical and CSF studies in the diagnosis of MS in patients presenting with partial Cervical Transverse Myelopathy and negative Cranial MRI
    Mult Scler 2000 Oct;6(5):312-6





#1

Fatigue And Declines In Cognitive Functioning In Multiple Sclerosis

Krupp LB, Elkins LE
Neurology 2000 Oct 10;55(7):934-9
State Univ of New York at Stony Brook, Dept of Neurology, Stony Brook, NY 11794-8121, USA
PMID# 11061247; UI# 20513425
Abstract

Objective
To determine whether Cognitive Fatigue, defined as a decline in Cognitive performance over a single testing session, could be identified in MS.

Methods
Forty-five individuals with MS and 14 healthy control participants completed a 4-hour session of Cognitive testing.

That involved a baseline NeuroPsychological battery, a continuous effortful Cognitive task (completing mental arithmetic problems administered on a computer), and a repeat NeuroPsychological battery.

Self-report measures of Fatigue and affect were completed before each step of the testing session.

Results
The pattern of change in Cognitive performances over the testing session significantly differed between the MS and control participants.

Individuals with MS showed declines on measures of verbal memory and conceptual planning, whereas the control participants showed improvement.

Although there were no significant differences between the groups on any of the baseline Cognitive measures, the MS participants performed worse than the control subjects.

On tests of Visual Memory, Verbal Memory, and Verbal Fluency that were repeated following the continuous effortful Cognitive task.

Both MS and control participants reported increased mental and physical Fatigue across the testing session compared with their baseline values.

Conclusion
Individuals with MS show declines in Cognitive Performance during a single testing session and fail to show the improvement exemplified by healthy control subjects.



#2

Cortical Evoked Potentials Of The Dorsal Nerve Of The Clitoris And Female Sexual Dysfunction In Multiple Sclerosis

Yang CC, Bowen JR, Kraft GH, Uchio EM, Kromm BG
J Urol 2000 Dec;164(6):2010-2013
Univ of Washington, Neurology, and Physical Medicine and Rehabilitation, Depts of Urology, Seattle, Washington
PMID# 11061904
Abstract

Purpose
We evaluated whether disrupting Genital Central Nervous System pathways is associated with subjective reports of Sexual Dysfunction in women with Multiple Sclerosis.

Materials And Methods
We performed Pudendal SomatoSensory Evoked Potential Testing in and had sexual questionnaires completed by 14 women with a mean age of 47 years who had Multiple Sclerosis.

Results
The mean Expanded Disability Status Scale was 5. All but 1 woman reported the desire for sexual intercourse. There was a high rate of dissatisfaction with their sex life and all study participants had concomitant Bladder and Bowel function problems.

The most common sexual complaint was difficult or no Orgasm, which was statistically associated with abnormalities or absence of 1 or both Pudendal Cortical Evoked Potentials. Fatigue and Arousal Disorders were also common.

Conclusions
Women with Multiple Sclerosis have a high self-reported rate of Sexual Dysfunction, which decreases quality of life.

ElectroDiagnostic data imply that Pudendal SomatoSensory innervation is necessary for normal female Orgasmic Function. More study is needed to confirm these findings.



#3

Significant Correlation Between IL-10 Levels And IgG Indices In Multiple Sclerosis CerebroSpinal Fluid

Nakashima I, Fujihara K, Misu T, Okita N, Takase S, Itoyama Y
J NeuroImmunol 2000 Nov 1;111(1-2):64-67
Tohoku Univ, School of Medicine, Dept of Neurology, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Japan
PMID# 11063822
Abstract

We measured the InterLeukin (IL-6) and IL-10 levels in the Plasma and the CerebroSpinal Fluid (CSF) of a total of 23 Relapsing Multiple Sclerosis (MS) patients

  • 18 with Conventional form of MS (C-MS)
  • 5 with Optic-Spinal form of MS (OS-MS)].

Using ELISA and correlated them with the IgG indices and OligoClonal IgG Bands (OB) to determine whether these Cytokines play a role in the Intrathecal ImmunoGlobulin production.

IL-10 values in the CSF significantly correlated with the IgG indices and tended to be higher in OB-positive patients.

In contrast, IL-10 values in the Plasma and IL-6 values in the CSF and the Plasma did not correlate with the IgG indices or OB.

The CSF-IL-10 value in OS-MS were much lower than those of C-MS, but those of CSF IL-6 did not differ between C-MS and OS-MS.

The results remained unchanged even when OS-MS patients were excluded. Our results may suggest a role of IL-10 in upregulating the Intrathecal IgIgG synthesis in Relapsing MS.



#4

Female Sex Steroids: Effects Upon Microglial Cell Activation

Drew PD, Chavis JA
J NeuroImmunol 2000 Nov 1;111(1-2):77-85
Univ of Arkansas for Medical Sciences, Dept of Anatomy, Slot 510, Shorey Bldg., Rm. 922, 4301 W. Markham St., 72205, Little Rock, AR, USA
PMID# 11063824
Abstract

Multiple Sclerosis occurs more commonly in females than males. However, the mechanisms resulting in gender differences in Multiple Sclerosis are unknown.

Activated Microglia are believed to contribute to Multiple Sclerosis pathology, perhaps in part due to production of Nitric Oxide (NO).

And TNF-alpha, molecules which can be toxic to cells including Oligodendrocytes.

The current study demonstrates that the female sex Steroids Estriol, ß-Estradiol and Progesterone inhibit LipoPolySaccharide (LPS) induction of Nitric Oxide (NO) production by primary rat Microglia and by the mouse N9 Microglial cell line.

These Hormones act by inhibiting the production of inducible Nitric Oxide Synthase (iNOS) which catalyses the synthesis of NO. Estriol likely inhibits iNOS Gene expression since the Hormone blocks LPS induction of iNOS RNA levels.

The pro-inflammatory Cytokines IFN-gamma and TNF-alpha are believed to be important modulators of Multiple Sclerosis.

Here, we demonstrate that Estrogens and Progesterone also inhibit NO production by Microglial Cells activated in response to these Cytokines. Activated Microglia elicit TNF-alpha in addition to NO.

And we further demonstrate that Estrogens and Progesterone repress Tumor Necrosis Factor-alpha production by these cells.

Finally, Estriol and Progesterone, at concentrations consistent with late pregnancy, inhibit NO and TNF-alpha production by activated Microglia.

Suggesting that Hormone inhibition of Microglial Cell activation may contribute to the decreased severity of Multiple Sclerosis symptoms commonly associated with pregnancy.



#5

Interferon-ß Treatment In Multiple Sclerosis Decreases The Number Of Circulating T-Cells Producing Interferon-gamma And InterLeukin-4

Furlan R, Bergami A, Lang R, Brambilla E, Franciotta D, Martinelli V, Comi G, Panina P, Martino G
J NeuroImmunol 2000 Nov 1;111(1-2):86-92
San Raffaele Scientific Institute, NeuroImmunology Unit-DIBIT, Dept . of NeuroScience, Via Olgettina 58, 20132, Milan, Italy
PMID# 11063825
Abstract

Systemic administration of Interferon-beta (IFN-ß) has been recently approved for the treatment of Relapsing/Remitting Multiple Sclerosis (RRMS).

The Immunological mechanism by which IFN-ß ameliorates MS is still partially unknown.

We measured the number of blood circulating CD4+, CD4-, CD8+, and CD8- T-Cells secreting IFN-gamma.

And IL-4 in 26 RRMS patients followed for up to 9 months of an alternate day s.c. treatment with 8x16 IU of IFN-ß-1b.

Compared to pre-treatment values, a significant (P<0.05) reduction of CD4+, CD4-, CD8+ and CD8- Cells producing IFN-gamma.

And of CD4+ and CD4- Cells producing IL-4 was observed in MS patients.

The IFN-ß-associated effect was evident soon after the beginning of the treatment and persisted for the entire follow-up period.

We did not observe any effect of IFN-ß treatment on the percentage of IL-4-producing CD8+ and CD8- Cells nor in that of Natural Killer (NK) Cells producing IFN-gamma.

Our results show that IFN-ß treatment in MS patients induces a profound and persistent down-regulation of the number of circulating T-Cells secreting IFN-gamma.

And IL-4 thus suggesting a broader rather than a specific ImmunoModulatory effect of IFN-ß in MS.



#6

VLA-4/CD49d Downregulated On Primed T-Lymphocytes During Interferon-ß Therapy In Multiple Sclerosis

Muraro PA, Leist T, Bielekova B, McFarland HF
J NeuroImmunol 2000 Nov 1;111(1-2):186-194
National Institutes of Health, National Institute of Neurological Disorders and Stroke, NeuroImmunology Branch, 10 Center Drive MSC1400, 20892-1400, Bethesda, MD, USA
PMID# 11063837
Abstract

Effects on Adhesion Molecules of Immune Cells might contribute to the mode of action of Interferon-beta (IFN-ß) in Multiple Sclerosis (MS).

We have serially monitored the cell surface expression of Integrins CD49d (VLA-4) and CD11a (LFA-1) on fresh T-Lymphocyte subpopulations from 5 MS patients monthly for 2 months prior to treatment and for 3 months on treatment with IFN-ß-1b.

In parallel, we assessed inflammatory disease activity by monthly contrast-enhanced Magnetic Resonance Imaging (MRI).

IFN-ß treatment specifically downregulated CD49d expression on CD8+ and CD4+/CD45RO+ 'memory' T-Lymphocytes.

And differentially modulated the proportion of CD4+, CD8+ and CD27+ T-Cells.

These effects may play an important role in the reduction of Central Nervous System cell trafficking and inflammation in MS.



#7

CD4+CD45RO+) CD49d (high) Cells Are Involved In The Pathogenesis Of Relapsing/Remitting Multiple Sclerosis

Barrau MA, Montalban X, Saez-Torres I, Brieva L, Barbera N, Martinez-Caceres EM
J NeuroImmunol 2000 Nov 1;111(1-2):215-223
Unitat de NeuroImmunologia Clinica, Servei de Neurologia, Hospital General Universitari Vall d'Hebron, Ps Vall d'Hebron 119-129, 08035, Barcelona, Spain
PMID# 11063841
Abstract

In the animal model of Multiple Sclerosis, Experimental AutoImmune EncephaloMyelitis, Encephalitogenic T-Cells differ from the non-Encephalitogenic ones in their expression of CD49d.

The disease-inducing CD49d (high) and not the CD49d (low) cells enter the Brain Parenchyma. In this context, we characterized CD4+ (CD45RO+ CD49d (high) cells in Relapsing/Remitting Multiple Sclerosis (RR-MS) patients.

These cells, showing characteristics of activated cells able to produce pro-inflammatory Cytokines, were found to be increased in peripheral blood during relapses and present in high numbers in CerebroSpinal Fluid.

These results suggest that the CD4+ CD45RO+ CD49d (high) subpopulation in RR-MS patients includes AutoReactive Cells and may be target for ImmunoTherapy.



#8

Pattern Of Cytokine Secretion By Peripheral Blood Cells Of Patients With Multiple Sclerosis In Brazil

da Costa PM, Yasuda CL, Scagliusi SM, Diaz-Bardales BM, Maciel E, Damasceno BP, SL Blotta MH, Tilbery CP, Santos LM
Mult Scler 2000 Oct;6(5):293-9
Institute of Biology, UNICAMP, Dept of Microbiology and Immunology, Campinas, Brazil
PMID# 11064437; UI# 20519921
Abstract

AutoImmune T-Cells play a key role as regulators and effectors of organ-specific AutoImmune Disease.

In Multiple Sclerosis (MS), activated T-Cells specific for Myelin components produce a plethora of inflammatory Cytokines and mediators that contribute to Myelin damage.

The production of ProInflammatory and regulatory Cytokines by peripheral blood cells from patients with active and stable MS and healthy controls were examined.

The results show that TNF-alpha production was somewhat elevated in active MS with no significant increase in the IFN-gamma level.

Whereas in the chronic phase the anti-inflammatory Cytokines IL-10 and TGFß increased, accompanied by a reduction in IFN-gamma when stimulated by Myelin Basic Protein.

Multiple Sclerosis (2000) 6 293 - 299



#9

Importance Of Paraclinical And CSF Studies In The Diagnosis Of MS In Patients Presenting With Partial Cervical Transverse Myelopathy And Negative Cranial MRI

Bashir K, Whitaker JN
Mult Scler 2000 Oct;6(5):312-6
Univ of Alabama at Birmingham, Dept of Neurology, Alabama, USA
PMID# 11064439; UI# 20519923
Abstract

Patients presenting with isolated partial Cervical Myelopathy are at high risk for development of Multiple Sclerosis (MS), especially if lesions suggestive of DeMyelination are present on Cranial Magnetic Resonance Imaging (MRI).

This risk is lower, though not precisely known, in patients whose Cranial MRI is normal. This clinical issue was addressed by examining the role of paraclinical studies in establishing a diagnosis of MS at the time of initial presentation.

Twelve consecutive patients, mean age of 32.2 years, seen over 6.5 years were identified prospectively and included in this study.

Numbness was the presenting symptom in 11 of these patients. Symptoms completely resolved in nine patients regardless of treatment with GlucoCorticoids.

Evoked Potential (EP) and CerebroSpinal Fluid (CSF) examinations assisted in establishing a diagnosis of Laboratory-Supported Definite (LSDMS) or Clinically Probable (CPMS) MS in six patients at the time of presentation.

During a clinical follow-up period of 4.1 years, four developed recurrent Neurologic deficits leading to the establishment of a diagnosis of Clinically Definite MS (CDMS).

The presence of a solitary, non-specific lesion on Cranial MRI resulted in an increased risk for the development of Definite MS.

In patients with a clinically isolated Cervical partial Transverse Myelitis (TM) and normal Cranial MRI, an accurate diagnosis of MS can usually be made. Revision of the diagnostic criteria for LSDMS is warranted.



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