MS Abstracts 7c-2g1

  1. Phagocytic properties of Microglia in vitro: Implications for a role in Multiple Sclerosis and EAE
    Microsc Res Tech 2001 Jul 15;54(2):81-94

  2. Clinical assessment of Sildenafil in the treatment of Neurogenic male Sexual Dysfunction: After the hype
    NeuroRehabilitation 2000;15(2):101-105

  3. Chemokines and their receptors in the Central Nervous System
    Front Neuroendocrinol 2001 Jul;22(3):147-84

  4. Therapeutic efficacy during active phases of Multiple Sclerosis: Gait analysis and comparison with the EDSS score
    Rev Neurol (Paris) 2001 Jul;157(6-7):649-654

  5. Myelopathy - Sjogren's Syndrome association: analysis of clinical and radiological findings and clinical course
    Rev Neurol (Paris) 2001 Jul;157(6-7):669-678

  6. Heat Shock Protein 60 in Corpora Amylacea
    Pathol Oncol Res 2001;7(2):140-4

  7. Measurement of Ataxic symptoms with a graphic tablet: standard values in controls and validity in Multiple Sclerosis
    J NeuroSci Methods 2001 Jul 15;108(1):25-37

  8. Acute Myelopathies: Clinical, laboratory and outcome profiles in 79 cases
    Brain 2001 Aug;124(Pt 8):1509-21

  9. Bacterial Peptidoglycan and Immune reactivity in the Central Nervous System in Multiple Sclerosis
    Brain 2001 Aug;124(Pt 8):1544-54

  10. Increased Serum levels of InterLeukin-18 in Multiple Sclerosis
    Neurology 2001 Jul 24;57(2):342-4


Phagocytic Properties Of Microglia In Vitro: Implications For A Role In Multiple Sclerosis And EAE

Smith ME
Microsc Res Tech 2001 Jul 15;54(2):81-94
VA Health Care Center, Dept of Neurology, Palo Alto, California 94304
PMID# 11455615; UI# 21348425

The Microglial Cell, after many years of neglect, has become recognized as the sole representative cell of the Immune System that resides in the normal Central Nervous System.

While normally dormant, Microglia can be activated by secretory substances or signals associated with disease or injury, and becomes a Phagocytic Cell, which also produces its own injurious molecules.

In the activating process, its Morphology is changed from a resting process-bearing cell, into a rounded Amoebic form.

And displays new or increased amounts of functional markers, such as receptors and Class I and Class II MHC molecules.

Microglia prepared from newborn mice or rats for tissue culture are already activated, and can be used for studies of their Phagocytic properties.

Although they can Phagocytize foreign substances, their uptake and metabolism of Myelin are emphasized here, in keeping with their role in DeMyelinating Diseases.

A number of receptors have been implicated and appear to be important in the attachment to, and ingestion of, Myelin particles in vitro, including the Fc, Complement, Macrophage scavenger, and the Galectin-3/MAC-2 receptors.

Although the alpha2-MacroGlobulin/low-density Lipoprotein receptor and Mannose receptors have also been suggested as participants in Myelin Phagocytosis.

Certain Cytokines and Adhesion Molecules also regulate the Phagocytic activity of Microglia.

Comparative in vitro studies of Phagocytosis by peritoneal Macrophages and Microglia have shown that the two kinds of cells respond differently to regulatory molecules.

And it is concluded that they have different innate properties.

The role of Microglia in the DeMyelinative Diseases Experimental AutoImmune EncephaloMyelitis and Multiple Sclerosis is emphasized here.

And the possible means of intervention in the process leading to Myelin destruction is discussed.

Microsc. Res. Tech. 54:81-94, 2001. Published 2001 Wiley-Liss, Inc.


Clinical Assessment Of Sildenafil In The Treatment Of Neurogenic Male Sexual Dysfunction: After The Hype

Green BG, Martin S
NeuroRehabilitation 2000;15(2):101-105
Shepherd Center, Atlanta, GA, USA
PMID# 11455087

To evaluate the efficacy and safety of Sildenafil over a two-year period in patients with Erectile Dysfunction caused by Spinal Cord Injury and Multiple Sclerosis.

In a clinical practice following FDA approval and release of the medication to the general healthcare community.

Study Design
40 patients including 33 SCI (13 Quadriplegics, 20 Paraplegics; 14 complete, 19 incomplete) and 7 MS patients were prescribed Sildenafil in varying dosages.

The patients were asked to return to the clinic for additional prescriptions so that we could assess their clinical response and their incidence of side effects.

They were then followed for a period of up to two years either by follow up clinic visits or telephone interviews.

To determine whether they continued to use Sildenafil as an ongoing solution to their Erectile Dysfunction.

Mean Erectile Response went from 4.9 to 7.8 (scale 1-10). Non-responders went from 9 to 4. 36 of the 40 were able to achieve erections sufficient for sexual intercourse.

At the 2-year interval 13 of the 40 were no longer using Sildenafil but only six discontinued due to lack of response.

Adverse effects were minimal and mimicked those seen in the able-bodied studies.

Sildenafil is a safe and effective first line treatment for the treatment of male Neurogenic Erectile Dysfunction.

However close clinical surveillance is necessary so that patients can avail themselves of other options should Sildenafil not be effective.


Chemokines And Their Receptors In The Central Nervous System

Bajetto A, Bonavia R, Barbero S, Florio T, Schettini G
Front Neuroendocrinol 2001 Jul;22(3):147-84
National Institute for Cancer Research, Pharmacology and NeuroScience, Genoa, Italy
PMID# 11456467; UI# 21349981

Chemokines are a family of proteins associated with the trafficking of Leukocytes in physiological Immune surveillance and inflammatory cell recruitment in host defence.

They are classified into four classes based on the positions of key cystiene residues: C, CC, CXC, and CX3C. Chemokines act through both specific and shared receptors that all belong to the superfamily of G-protein-coupled receptors.

Besides their well-established role in the Immune System, several recent reports have demonstrated that these proteins also play a role in the Central Nervous System (CNS).

In the CNS, Chemokines are constitutively expressed by Microglial Cells, Astrocytes, and Neurons, and their expression can be increased after induction with inflammatory mediators.

Constitutive expression of Chemokines and Chemokine receptors has been observed in both developing and adult Brains.

And the role played by these proteins in the normal Brain is the object of intense study by many research groups.

Chemokines are involved in Brain development and in the maintenance of normal Brain homeostasis; these proteins play a role in the migration, differentiation, and proliferation of Glial and Neuronal Cells.

The Chemokine Stromal cell-derived factor 1 and its receptor, CXCR4, are essential for life during development.

And this Ligand-receptor pair has been shown to have a fundamental role in Neuron migration during Cerebellar formation.

Chemokine and Chemokine receptor expression can be increased by inflammatory mediators, and this has in turn been associated with several acute and chronic inflammatory conditions.

In the CNS, Chemokines play an essential role in NeuroInflammation as mediators of Leukocyte infiltration.

Their overexpression has been implicated in different Neurological Disorders, such as Multiple Sclerosis, Trauma, Stroke, Alzheimer's Disease, tumor progression, and Acquired Immunodeficiency Syndrome-Associated Dementia.

An emerging area of interest for Chemokine action is represented by the communication between the NeuroEndocrine and the Immune System.

Chemokines have Hormone-like actions, specifically regulating the key host PhysioPathological responses of fever and appetite.

It is now evident that Chemokines and their receptors represent a plurifunctional family of proteins whose actions on the CNS are not restricted to NeuroInflammation.

These molecules constitute crucial regulators of cellular communication in physiological and developmental processes.

Copyright 2001 Academic Press.


Therapeutic Efficacy During Active Phases Of Multiple Sclerosis: Gait Analysis And Comparison With The EDSS Score

Fauchard-Renard C, Renard JF, Miret N, Hannequin D, Mihout B, Weber J
Rev Neurol (Paris) 2001 Jul;157(6-7):649-654
Federation des Sciences Neurologiques
PMID# 11458184

Fifteen patients experiencing a flare-up of Multiple Sclerosis were given 1 g MethylPrednisolone per day for 5 days.

The EDSS score and Gait analysis using Spatio-Temporal variables were recorded for these patients on days 0, 5 and 45.

Both methods evidenced significant improvement but the significance was observed between day 0 and day 5 for the EDSS and between day 5 and 45 for gait speed and between day 0 and 45 for step rate.

Gait speed was correlated with the Pyramidal Scale but not with the other Functional Scales of the EDSS.

These results suggest that EDSS and Spatio-Temporal Gait analysis are different tools for the assessment of therapeutic effect.

Gait analysis can provide a precise quantitative assessment of the locomotor handicap as a function of the proposed treatment.


Myelopathy - Sjogren's Syndrome Association: Analysis Of Clinical And Radiological Findings And Clinical Course

De Seze J, Stojkovic T, Hachulla E, Breteau G, Michon-Pasturel U, Mounier-Vehier F, Hatron PY, Vermersch P
Rev Neurol (Paris) 2001 Jul;157(6-7):669-678
CHRU de Lille
Service de Neurologie, Hopital R. Salengro,
PMID# 11458186

Myelopathies associated with Sjogren's Syndrome has been rarely described especially concerning Magnetic Resonance Imaging (MRI) and treatment aspects.

The aim of this study was to determine the clinical, laboratory and radiological features of Myelopathies occuring in Sjogren's Syndrome.

Eleven patients were studied, 7 with an acute Myelopathy and 4 with a chronic form. Acute Myelopathy were clinically severe with a feature of Transverse Myelitis necessiting ImmunoSuppressive drugs.

On the other hand, chronic forms were closely similar to Progressive Multiple Sclerosis (MS), for clinical and laboratory data.

In 7 cases Optic Neuritis was found associated with Myelopathy and fulfilled the diagnostic criteria of Devic's Syndrome in 4 cases.

The diagnosis of Myelopathy associated with Sjogren's Syndrome may be difficult especially compared with MS, HTLV1 or HIV Myelopathy and Sarcoidosis, in the chronic form but also with other Vasculitis, MS or Viral infection in the acute forms.

However, in this last form, Magnetic Resonance Imaging and CerebroSpinal Fluid data should bring to the diagnosis of Sjogren Syndrome and confirmed by appropriate tests.

This diagnosis will have direct consequences for an early treatment by ImmunoSuppressive drugs.


Heat Shock Protein 60 In Corpora Amylacea

Gati I, Leel-Ossy L
Pathol Oncol Res 2001;7(2):140-4
Univ, Medical School, Pecs, Dept of Neurology Ret u. 2., Pecs, H-7623, Hungary, (36) 72 314 344
PMID# 11458278; UI# 21351352

Heat Shock Protein 60 representation in the Corpora Amylacea of the Brain was investigated in five different Neurological Diseases.

In the cases with Cerebral Infarct, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, Acute Disseminated EncephaloMyelitis and Primary Tumors of the Nervous System.

The Corpora Amylacea showed similar appearance with strong HSP-60 positivity in all investigated disorders at the predilection sites.

In the inflammatory diseases, besides Corpora Amylacea, several cellular elements exhibited HSP-60 ImmunoStaining too.

In these cases, the widespread HSP-60 ImmunoReactivity associated with relative moderate Corpora Amylacea production as compared to other diseases.

From this contradiction we concluded the Corpora Amylacea participate in the cellular stress reaction but Stress Protein synthesis certainly is not the primary event in Corpora Amylacea formation.

In the development of the Corpora Amylacea the incipient process is most probably degenerative in nature.

Which later on is accompanied by Stress Protein synthesis and slow growing of these round structures designated for a protective role in the Brain.

However, the role of the Stress Protein synthesis in the Corpora Amylacea formation and growth was not unequivocally answered in this study.

It is necessary to perform further comparative investigations of the Stress Protein representation and Corpora Amylacea formation.

In different diseases which may help in discovering useful PathoGenetic data and the biological role of this degenerative structure.


Measurement Of Ataxic Symptoms With A Graphic Tablet: Standard Values In Controls And Validity In Multiple Sclerosis

Erasmus L, Sarno S, Albrecht H, Schwecht M, Pollmann W, Konig N
J NeuroSci Methods 2001 Jul 15;108(1):25-37
Marianne-Strauss-Klinik, Berg-Kempfenhausen, Milchberg 21, D-82335 Berg, Germany
PMID# 11459615; UI# 21352920

Aim of our study was to find a specific measure for the intensity of upper limb Tremor and other Ataxic symptoms in Multiple Sclerosis (MS) patients, and to establish standard values and test quality parameters.

Three hundred and forty-two consecutive patients with different symptoms in the upper limbs (Upper Motor Neuron symptoms, Cerebellar upper limb Ataxia, and/or Sensory deficits in the upper limbs) and 140 healthy controls took part in the study.

All patients and controls had to trace over a 25 cm high figure '8' on a graphic tablet, to tap with the stylus on the tablet and to perform the Nine-Hole-Peg Test (9HPT).

Patients were additionally examined using clinical standard scales to classify Motor dysfunctions of the upper limbs.

One hundred and eighty-nine patients and 27 controls were tested twice to investigate the test reliability.

Kinematic analysis of the tablet data was performed by kernel estimators, Oscillatory activity by Spectral analysis.

Total power in the 2-10 Hz band was very specific for Ataxia versus other Motor symptoms.

Tapping and 9HPT could well distinguish patients from controls, and patients with predominant Motor Neuron or Cerebellar symptoms from patients with predominant Sensory dysfunctions.

Mean drawing error did not differ between Motor and Sensory dysfunctions. The test-retest reliability was similarly high for both Spectral analysis and 9HPT.


Acute Myelopathies: Clinical, Laboratory And Outcome Profiles In 79 Cases

de Seze J, Stojkovic T, Breteau G, Lucas C, Michon-Pasturel U, Gauvrit JY, Hachulla E, Mounier-Vehier F, Pruvo JP, Leys D, Destee A, Hatron PY, Vermersch P
Brain 2001 Aug;124(Pt 8):1509-21
CHU de Lille, Dept of Neurology, Dept of NeuroRadiology and Dept of Internal Medicine, Dept of Neurology, CH de Lens, France
PMID# 11459743; UI# 21352630

The main etiologies of Acute Myelopathy (AM) are: Multiple Sclerosis, Systemic Disease (SD), Spinal Cord Infarct (SCI), ParaInfectious Myelopathy (PIM) and Delayed Radiation Myelopathy (DRM).

Although a large amount of data have been published for each individual Etiology, comparison studies are scarce. The aim of this study was to assess the various Etiological and outcome profiles of AM.

We studied 79 cases: 34 (43%) in Multiple Sclerosis; 13 (16.5%) in SD; 11 (14%) in SCI; five (6%) in PIM; and three (4%) in DRM.

Myelopathies were of unknown origin in 13 (16.5%) patients. We evaluated clinical, Spinal Cord and Brain MRI, CSF and Evoked Potentials data at admission, MRI outcome at 6 months and clinical outcome at 12 months.

A statistical comparison of clinical, laboratory and outcome data was only performed between Multiple Sclerosis, SD and SCI patients due to the small number of cases in the other groups.

A motor deficit was more frequent in SD and SCI than in Multiple Sclerosis where initial symptoms were predominantly Sensory (P < 0.001).

Spinal Cord MRI showed Lateral or Posterior lesions of less than two Vertebral levels in Multiple Sclerosis, in contrast to SD and SCI, where lesions involved more Vertebral levels and were CentroMedullar (P < 0.001).

Brain MRI was most frequently abnormal in Multiple Sclerosis (68%), but was also abnormal in 31% of SD patients (P < 0.05).

OligoClonal Bands in CSF were more frequent in Multiple Sclerosis than in SD (P < 0.001) and were never found in SCI.

Clinical outcome at 12 months was good in 88% of Multiple Sclerosis cases, and poor or fair in 91% of SCI and 77% of SD.

Etiologies of AM may be differentiated on the basis of clinical, Spinal Cord and Brain MRI, CSF and outcome data, and allow a probable diagnosis to be made in previously undetermined cases.

These findings may have therapeutic implications for cases with a questionable diagnosis.


Bacterial PeptidoGlycan And Immune Reactivity In The Central Nervous System In Multiple Sclerosis

Schrijver IA, van Meurs M, Melief MJ, Wim Ang C, Buljevac D, Ravid R, Hazenberg MP, Laman JD
Brain 2001 Aug;124(Pt 8):1544-54
Rotterdam and Netherlands Brain Bank, Erasmus Univand Univ Hospital Rotterdam-Dijkzigt, Depts of Immunology and Neurology, Amsterdam, The Netherlands
PMID# 11459746; UI# 21352633

Multiple Sclerosis is believed to result from a CD4+ T-Cell response against Myelin Antigens.

PeptidoGlycan, a major component of the Gram-positive Bacterial Cell Wall, is a functional LipoPolySaccharide analogue with potent ProInflammatory properties and is conceivably a mediator of sterile inflammation.

Here we demonstrate that PeptidoGlycan is present within Antigen-Presenting Cells in the Brain of Multiple Sclerosis patients.

These cells have Macrophage and Dendritic Cell characteristics, and are ImmunoCompetent as evidenced by co-expression of inflammatory Cytokines and co-stimulatory molecules.

In addition, Intrathecal Plasma Cells specific for PeptidoGlycan are present in Multiple Sclerosis Brain tissue, and AntiBodies binding PeptidoGlycan are present in CSF during active disease.

PeptidoGlycan may thus contribute to T- and B-Cell activity during Brain inflammation without a requirement for local Bacterial replication.


Increased Serum Levels Of InterLeukin-18 In Multiple Sclerosis

Nicoletti F, Di Marco R, Mangano K, Patti F, Reggio E, Nicoletti A, Bendtzen K, Reggio A
Neurology 2001 Jul 24;57(2):342-4
Institute of Microbiology, Univ of Milan Bicocca
PMID# 11468327; UI# 21361680

Serum but not CSF concentrations of the Interferon-gamma-inducing Cytokine InterLeukin-18 (IL-18) were significantly augmented in patients with MS as compared to both healthy controls and patients with other Neurologic Diseases.

Patients with MS with Chronic Secondary/Progressive disease had significantly higher Serum levels than those with Relapsing/Remitting MS.

In the latter group, IL-18 levels were higher in patients with acute exacerbation as compared to those with stable disease.

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