MS Abstracts 02b-2g1

  1. Effects of grating spatial orientation on Visual Evoked Potentials and contrast sensitivity in Multiple Sclerosis
    Acta Neurol Scand 2001 Feb;103(2):97-104

  2. DeMyelination and Axonal damage in a non-human primate model of Multiple Sclerosis
    J Neurol Sci 2001 Feb 15;184(1):41-49

  3. The Oligodendrocyte precursor cell in health and disease
    Trends NeuroSci 2001 Jan 1;24(1):39-47

  4. Comparison of Memory performance in Relapsing/Remitting, Primary/Progressive and Secondary/Progressive Multiple Sclerosis
    NeuroPsychiatry NeuroPsychol Behav Neurol 2001 Jan;14(1):32-44

  5. MTR Histogram analysis of Gray Matter in Relapsing/Remitting Multiple Sclerosis
    AJNR Am J NeuroRadiol 2001 Mar;22(3):470-475

  6. Natural killer type 2 bias in remission of Multiple Sclerosis
    J Clin Invest 2001 Mar 1;107(5):R23-R29

  7. CTLA-4 in Multiple Sclerosis - lack of Genetic association in a European Caucasian population but evidence of interaction with HLA-DR2 among Shanghai Chinese
    J Neurol Sci 2001 Mar 1;184(2):143-147

  8. Polyspecific ImmunoGlobulins (IVIg) suppress proliferation of human (auto)antigen-specific T-Cells without inducing apoptosis
    J NeuroImmunol 2001 Mar 1;114(1-2):160-167

  9. Chemokine Receptor expression on T-Cells in blood and CerebroSpinal Fluid at relapse and remission of Multiple Sclerosis: imbalance of Th1/Th2-associated chemokine signaling
    J NeuroImmunol 2001 Mar 1;114(1-2):207-212

  10. Complete bilateral horizontal gaze paralysis disclosing Multiple Sclerosis
    J Neurol NeuroSurg Psychiatry 2001 Feb;70(2):252-255

  11. ImmunoGlobulin G heavy chain repertoire in Multiple Sclerosis plaques is distinct from the heavy chain repertoire in peripheral blood Lymphocytes
    Clin Immunol 2001 Feb;98(2):258-263


Effects Of Grating Spatial Orientation On Visual Evoked Potentials And Contrast Sensitivity In Multiple Sclerosis

Logi F, Pellegrinetti A, Bonfiglio L, Baglini O, Siciliano G, Ludice A, Sartucci F
Acta Neurol Scand 2001 Feb;103(2):97-104
Univ of Pisa, Institute of Neurology, Dept of NeuroSciences, Pisa, Italy
PMID# 11227139; UI# 21118710

Previous studies suggest a delay of Pattern Visual Evoked Potentials (PVEPs) in Multiple Sclerosis (MS) depending on grating orientation.

We examined a group of 14 patients with Definite MS recording PVEPs to vertical and horizontal grating and analyzing latency and amplitude of P60, N70 and P100 waves.

We evaluated Contrast Sensitivity (CS) to dark and bright bars of several Spatial Frequencies (SF). The aim was to evaluate the diagnostic value of Evoked Responses and CS in revealing involvement of Cortical structures.

PVEPs to 1 degrees cycle/degree (c/d) vertical bars were abnormal in 25% for P60, in 32% for N70 and in 36%, for P100; in 25%, 36% and 42% respectively at 4 c/d.

As regards horizontal bars at 1 c/d we found alterations of P60, N70 and P100 in 11%, 19% and 27% respectively; at 4 c/d in 19%, 27%) and 35%.

CS resulted more abnormal for vertical grating, with a maximum impairment for 3.7 c/d SF.

We may conclude that the use of vertical grating in clinical routine is more reliable both for PVEPs and CS testing; in addition CS can be abnormal even with normal PVEPs.

This could mean an early impairment of CS and provide useful indications about a subclinical involvement of Visual Cortex.


DeMyelination And Axonal Damage In A Non-Human Primate Model Of Multiple Sclerosis

Mancardi G, Hart B, Roccatagliata L, Brok H, Giunti D, Bontrop R, Massacesi L, Capello E, Uccelli A
J Neurol Sci 2001 Feb 15;184(1):41-49
Univ of Genoa, Dept of Neurological Sciences and Vision, Via De Toni 5, 16132, Genoa, Italy
PMID# 11231031

The DeMyelinating plaque is the paradigmatic lesion of Multiple Sclerosis (MS), but only recently attention has been given to Axonal Damage and to its role in the pathophysiology of disease.

Albeit the possible relevance of Axonal loss in MS and its experimental models, the amount and timing of Axonal sufferance has been addressed only in Experimental AutoImmune EncephaloMyelitis (EAE) of rodents.

In this report we observed that, in the marmoset model of EAE, Axonal damage occurs early during the DeMyelinating process as assessed by ImmunoReactivity for Amyloid Precursor Protein (APP).

And NonPhosphorylated NeuroFilaments (SMI-32 positive) detected mostly in early active lesions compared to late active and Normal-Appearing White Matter.

The rare occurrence of Morphological features of Axonal transection, such as APP or SMI-32 positive spheroids and swellings, as well as an increase of NeuroFilament density in the DeMyelinated Axons.

Without accumulation of electron dense Organelles or Osmiophilic bodies, at electron microscopy, suggests that early Axonal damage may be, at least in part, a reversible process.

These findings are of relevance for the development of therapies, which can protect Axons and enhance their function and survival.


The Oligodendrocyte Precursor Cell In Health And Disease

Levine JM, Reynolds R, Fawcett JW
Trends NeuroSci 2001 Jan 1;24(1):39-47
SUNY, Dept of NeuroBiology and Behavior, 11794, Stony Brook, NY, USA
PMID# 11163886

Adult Oligodendrocyte Precursor Cells (OPCs) make up around 5-8% of the Glial Cell population in the CNS.

Their function in the undamaged CNS is largely unknown, but their processes are in contact with Nodes of Ranvier and Synapses, suggesting a regulatory role at these structures.

The cells divide slowly, and constitute approximately 70% of cells labelled following a pulse injection of BromodeoXyuridine.

In the injured CNS the cells form a reactive Glial population that undergoes hypertrophy and mitosis, probably driven by a variety of growth factors and Cytokines.

In response to DeMyelination they divide and are thought to differentiate to provide new Oligodendrocytes to replace those that have been lost.

However, ReMyelination fails during the later stages of Multiple Sclerosis, and it is not clear whether this is as a result of a depletion of adult OPCs, inhibition within the Glial scar, or damage to the Axons that prevents Myelination.

Adult OPCs are also activated and proliferate following other forms of CNS damage, such as mechanical injury, ExcitoToxicity and Viral infection. The cells produce several of the Chondroitin Sulphate Proteoglycans that might inhibit Axon regeneration.


Comparison Of Memory Performance In Relapsing/Remitting, Primary/Progressive And Secondary/Progressive Multiple Sclerosis

Gaudino EA, Chiaravalloti ND, DeLuca J, Diamond BJ
NeuroPsychiatry NeuroPsychol Behav Neurol 2001 Jan;14(1):32-44
Kessler Medical Rehabilitation Research and Education Corp., West Orange, New Jersey 07052, USA
PMID# 11234907; UI# 21129559

The current investigation was designed to examine the influence of disease course on the specific patterns of Acquisition and Retrieval Impairments in Multiple Sclerosis (MS).

Recent investigations of Learning and Memory in MS have shown that many subjects have Impaired Verbal and Visual New Learning Abilities, but normal long-term recall and recognition.

However, heterogeneity in the Learning and Memory abilities of subjects has been documented. Some evidence in the literature suggests that this heterogeneity may be in part attributable to clinical variables, such as disease course.

Verbal and Visual learning and Memory tests, modified to equate MS groups with healthy controls on initial acquisition of information, were administered to

  1. 64 individuals with Clinically Definite MS:
    • Relapse/Remitting = 21
    • Primary/Progressive = 18
    • Secondary/Progressive = 25
  2. 20 healthy control participants

Recall and recognition performance then was evaluated at 30 minutes, at 90 minutes, and at 1 week for the verbal learning task, and at 30 minutes and at 90 minutes for the Visual learning task.

Results indicate that the two Progressive forms of MS result in significantly greater deficits in regard to the acquisition of New Verbal information, with the Secondary/Progressive group showing a significantly higher failure rate in regard to meeting the learning criterion.

Performance for recognition measures was not significantly different among groups, whereas Recall Performance of the Primary/Progressive group was significantly below that of the control group and of the Secondary/Progressive group.

When testing new learning with VisuoSpatial information, individuals with Relapsing/Remitting MS and Secondary/Progressive MS required more trials than control participants to learn the same amount of Visual information.

Visual Recall and Recognition performance did not differ between groups. No group differences in rates of forgetting for VisuoSpatial material was observed after equating for acquisition.

Results of the current study indicate that the primary problem in MS with regard to Memory functioning is in the acquisition of new information.

Our findings support previous research showing Verbal Memory Deficits with a Progressive disease course and VisuoSpatial Memory Deficits in Relapsing/Remitting MS.

However, the detailed analysis of new learning and memory performed in the current study, indicated that the Primary/Progressive group, may be showing difficulty in their ability to use newly learned information.

The pattern of new learning deficits observed between MS disease subtypes in the current study was determined to be unrelated to the duration of MS and to the physical severity of the disease.

The degree of physical disability observed in patients with MS, does not appear to be related to the degree of Cognitive decline.

Because of the distinct patterns and severity of Memory Dysfunction noted within each disease type, independent of physical disability.


Magnetization Transfer Ratio Histogram Analysis Of Gray Matter in Relapsing/Remitting Multiple Sclerosis

Ge Y, Grossman RI, Udupa JK, Babb JS, Kolson DL, McGowan JC
AJNR Am J NeuroRadiol 2001 Mar;22(3):470-475
Fox Chase Cancer Center, Depts of, Radiology (Y.G., R.I.G., J.K.U., J.C.M.) and Neurology (D.L.K.), Hospital of the Univ of Pennsylvania, and Dept of Biostatistics (J.S.B.), Philadelphia, PA
PMID# 11237968; UI# 21133865

Background And Purpose
Gray Matter may be affected by Multiple Sclerosis (MS), a White Matter disease. Magnetization Transfer Ratio (MTR) is a sensitive and quantitative marker for structural abnormalities, and has been used frequently in the imaging of MS.

In this study, we evaluated the amount of MTR of Gray Matter among patients with Relapsing/Remitting MS and healthy control subjects as well as the correlation between Gray Matter MTR abnormality and Neurologic disability associated with Relapsing/Remitting MS.

We obtained fast Spin-Echo dual-echo and Magnetization Transfer (with and without MT saturation pulses) images from eighteen patients with Relapsing/Remitting MS and 18 age-matched healthy control subjects.

Gray Matter was segmented using a semiautomated system. Gray Matter MTR Histogram parameters, Kurtzke Expanded Disability Status Scale (EDSS), total T2 lesion volume, and Gray Matter volumes were obtained for statistical analysis.

A significant difference was found in Gray Matter MTR between patients with Relapsing/Remitting MS and healthy subjects (mean and median).

Gray Matter MTR Histogram normalized peak heights in patients inversely correlated with EDSS (r = -0.65, P: =.01). There was also an inverse correlation between mean MTR of Gray Matter and total T2 lesion volume.

The MTR of Gray Matter significantly differed between patients with Relapsing/Remitting MS and healthy control subjects, suggesting that MS is a more diffuse disease affecting the whole Brain, and Neuronal damage accumulates in step with T2 lesion volume.

Our finding of the relationship between Gray Matter MTR and EDSS indicates that measurement of Gray Matter abnormality may be a potentially useful tool for assessing clinical disability in MS.


Natural Killer Type 2 Bias In Remission Of MS

Takahashi K, Miyake S, Kondo T, Terao K, Hatakenaka M, Hashimoto S, Yamamura T
J Clin Invest 2001 Mar 1;107(5):R23-R29
National Institute of NeuroScience, National Center of Neurology and Psychiatry, Dept of Immunology, Kodaira; Tsukuba Primate Center for Medical Science, Ibaraki; and Tenri Hospital, Dept of Neurology, Nara, Japan
PMID# 11238569

Multiple Sclerosis (MS) is an AutoImmune Disease characterized by clinical relapse and remission.

Because of the potential role of Natural Killer (NK) Cells in the regulation of AutoImmunity, we have examined Cytokine profile and surface phenotype of NK Cells in the peripheral blood of MS.

Here we demonstrate that NK Cells in the remission of MS are characterized by a remarkable elevation of IL-5 mRNA and a decreased expression of IL-12Rbeta2 mRNA, as well as a higher expression of CD95.

Moreover, the NK Cells from MS in remission produced much larger amounts of IL-5 than did those from controls after stimulation with Phorbol Myristate Acetate (PMA) and Ionomycin.

These features are reminiscent of those of NK type 2 (NK2) Cells that can be induced in a condition favoring functional deviation of T-Cells toward Th2.

Remarkably, the NK Cells lose the NK2-like property when relapse of MS occurs, but regain it after recovery.

We also found that NK2 Cells induced in vitro inhibit induction of Th1 Cells, suggesting that the NK2-like cells in vivo may also prohibit AutoImmune effector T-Cells. Taken together, it is possible that NK Cells play an active role in maintaining the remission of MS.


CTLA-4 In Multiple Sclerosis. Lack Of Genetic Association In A European Caucasian Population But Evidence Of Interaction With HLA-DR2 Among Shanghai Chinese

Rasmussen HB, Kelly MA, Francis DA, Clausen J
J Neurol Sci 2001 Mar 1;184(2):143-147
Roskilde University, Dept of Life Sciences, PO Box 260, DK-4000, Roskilde, Denmark
PMID# 11239948

In the present study we searched for an association between Multiple Sclerosis (MS) and the Gene encoding the CytoToxic T-Lymphocyte Antigen 4 (CTLA-4).

Our experimental approach involved amplification of DNA fragments of the promoter and Exon 1 of this Gene containing single Nucleotide Polymorphisms followed by treatment of the amplified fragments with restriction Enzymes for Allele determination.

Included in the study were 84 MS patients and 125 healthy control subjects from a population of white caucasians. We also examined 42 MS patients and 86 healthy control subjects of Shanghai Chinese origin.

Significant differences in the distribution of GenoTypes or HaploTypes of the CTLA-4 Gene were not observed between MS patients and control subjects in either of the two populations (P>0.05).

Moreover, we were not able to confirm a previous finding of an association between Relapsing/Remitting MS and the heterozygous GenoType A/G of CTLA-4 Exon 1.

There was no evidence to suggest that interaction between HLA-DR2 and CTLA-4 is involved in the development of MS among European caucasians (P>0.05).

Opposed to this, analysis of the Shanghai Chinese suggested presence of such interaction (P=0.02). Our results do not support the assumption that CTLA-4 influences susceptibility to MS in European caucasians.

On the other hand, they raise the possibility that the development of MS in other ethnic groups involves interaction between CTLA-4 and DR2.


Polyspecific ImmunoGlobulins (IVIg) Suppress Proliferation Of Human (Auto)Antigen-Specific T-Cells Without Inducing Apoptosis

Aktas O, Waiczies S, Grieger U, Wendling U, Zschenderlein R, Zipp F
J NeuroImmunol 2001 Mar 1;114(1-2):160-167
Univ Hospital Charite, Division of NeuroImmunology, Dept of Neurology, NWFZ 2680, SchumannstraBe 20/21, 10117, Berlin, Germany
PMID# 11240027

Polyspecific ImmunoGlobulins (IVIg) have been shown to reduce disease activity in Multiple Sclerosis (MS).

To investigate the mechanisms of action of IVIg, we studied the impact of IVIg on growth and death (Apoptosis) of human (Auto)Antigen-specific T-Cells.

We observed a substantial suppression of proliferation of specifically activated T-Cells, in absence of Caspase activation or DNA fragmentation.

Further, neither susceptibility of T-Cells to undergo CD95-mediated Apoptosis nor expression of Apoptosis-blocking bcl-2 was modulated by IVIg.

We conclude that IVIg may inhibit the reactivity of Antigen-specific T-Cells in MS through suppression of proliferation rather than modulation of Apoptosis.


Chemokine Receptor Expression On T-Cells In Blood And CerebroSpinal Fluid At Relapse And Remission Of Multiple Sclerosis: Imbalance of Th1/Th2-Associated Chemokine Signaling

Misu T, Onodera H, Fujihara K, Matsushima K, Yoshie O, Okita N, Takase S, Itoyama Y
J NeuroImmunol 2001 Mar 1;114(1-2):207-212
Tohoku Univ, School of Medicine, Dept of Neurology, 1-1 Seiryo-Machi, Aoba-ku, 980-8574, Sendai, Japan
PMID# 11240033

The expression of Chemokine Receptors on Lymphocytes in the blood and CSF of Multiple Sclerosis (MS) patients was analyzed at relapse and remission.

Both CD4+ and CD8+ cells in CSF at relapse were enriched for Th1-type Receptors CXCR3 and CCR5 expression, and were reduced for Th2-type Receptors CCR3 and CCR4 expression compared with those of the blood.

CCR1 and CCR2 expressions on T-Cells were increased in CSF and blood, respectively. At remission, CCR5 expression, but not CXCR3 expression, was reduced in CSF CD4+ cells.

A biased Th1/Th2 balance may play a critical role in active inflammation and CCR5 on CSF CD4+ cells is a good marker of the disease activity.


Complete Bilateral Horizontal Gaze Paralysis Disclosing Multiple Sclerosis

Milea D, Napolitano M, Dechy H, Le Hoang P, Delattre JY, Pierrot-Deseilligny C
J Neurol NeuroSurg Psychiatry 2001 Feb;70(2):252-255
Hopital de la Pitie-Salpetriere, Dept of Ophthalmology, Paris, France
PMID# 11160480

Two women presented with Bilateral InterNuclear Ophthalmoplegia evolving in a few days to complete bilateral horizontal Gaze Paralysis. Convergence and vertical Eye movements were normal.

Cerebral MRI showed a few small White Matter lesions in the Lateral Ventricle regions, and, at the BrainStem level, a single, small, bilateral lesion affecting the posterior part of the Medial Pontine Tegmentum and responsible for the clinical syndrome.

The condition gradually improved in both patients, following a similar progression as at the onset: improvement first involved the adduction movements in both Eyes.

Whereas bilateral abduction Paresis still persisted for a few weeks, before complete recovery of Eye movements.

Bilateral damage to the Medial Longitudinal Fasciculus and subsequent lateral extent of damage to the region of the two emerging Abducen Fibers may explain the clinical findings. In both cases, the cause was probably Multiple Sclerosis.


The ImmunoGlobulin G Heavy Chain Repertoire In Multiple Sclerosis Plaques Is Distinct From The Heavy Chain Repertoire In Peripheral Blood Lymphocytes

Owens GP, Burgoon MP, Anthony J, Kleinschmidt-DeMasters BK, Gilden DH
Clin Immunol 2001 Feb;98(2):258-263
Univ of Colorado Health Sciences Center, Dept of Neurology, Denver, Colorado, 80262
PMID# 11161983

Analyzes have shown that the repertoire of Ig heavy chain sequences (VH) expressed in Multiple Sclerosis (MS) plaques or CerebroSpinal Fluid is consistent with B-Cell clonal expansion and affinity maturation.

PCR amplification of VH sequences from MS lesions obtained from an acute MS patient at autopsy revealed OligoClonal and extensively mutated VH sequences from plaque-periplaque regions.

With discrete intraclonal differences indicative of B-Cell clonal expansion in the groups of overrepresented major sequences.

None of the VH sequences expressed in plaque regions were detected in peripheral blood Lymphocytes from this patient. These data indicate the presence of a CNS-targeted Antigen-driven response in MS plaques.

Copyright 2000 Academic Press.

Medical Texts
Anatomy | Immune System | Lymphocytes | Meds
MHC | Movement | Cranial Nerves | Physiology

MS Glossary ThJuland's MSers' Glen - Our CyberHome Page Top The Glen's Gallery: Come & Share Our Stories MS Files MS Abstracts Site Index

ANS | Bladder | Cognition | Fatigue | Fluid | Genetics
Interferons | IVIG | Nitric Oxide | Optic Neuritis | Pain
Physiology | Prions | Prognosis | ReMyelinate | Steroids
Stress | Treatments | TNF | Uric Acid | Viruses

Copyright 1997 - 2011:
Permission is granted to MS Societies and all MSers to utilize information from these pages provided that no financial reward is gained and attribution is given to the author/s.