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Multiple Sclerosis Abstracts

  1. Health promotion practices of women with Multiple Sclerosis

  2. Medication use during pregnancy for neurologic conditions

  3. Treatment of AutoImmune Diseases through manipulation of Antigen Presentation

  4. T-Cell Receptor peptides as Immunotherapy for AutoImmune Disease

  5. Initiation and regulation of CNS AutoImmunity

  6. Assessment of Depression in patients with Neurologically disabling illnesses

  7. Modulation of T-Cell-Endothelial adhesion by Astrocyte conditioned medium

  8. Magnetic Resonance Spectroscopy of chronic Cerebral White Matter Lesions and Normal-Appearing White Matter in Multiple Sclerosis

  9. Antiviral immune responses modulate the nature of Central Nervous System (CNS) disease in a murine model of Multiple Sclerosis

  10. The infection of mouse by Theiler's Virus: from Genetics to Immunology

  11. A replicated prospective investigation of life stress, coping, & depressive symptoms In Multiple Sclerosis

  12. Managing side-effects of Interferon-beta in patients with Relapsing/Remitting Multiple Sclerosis

  13. Rationale for early treatment with Interferon beta-1a in Relapsing/Remitting Multiple Sclerosis

  14. Mood disturbance versus other symptoms of Depression in Multiple Sclerosis

  15. Problem solving by patients with Multiple Sclerosis: comparison of performance on the Wisconsin and California Card Sorting Test

  16. Isolated Cranial Nerve Palsies in Multiple Sclerosis

  17. Age at immigration to England of Asian & Caribbean Immigrants & the risk of developing Multiple Sclerosis

  18. The detection of Intrathecal synthesis of anti-herpes simplex IgG AntiBodies

  19. Dystonia as an isolated symptom of Multiple Sclerosis

  20. Pudendal Nerve Somatosensory Evoked Potentials in Probable Multiple Sclerosis

  21. Neurologic changes in patients with Multiple Sclerosis

  22. Fast Spin Echo & Fast Fluid Attenuated inversion recovery Sequences in Multiple Sclerosis

  23. Diagnostic importance of Middle Latency Auditory Evoked Potentials in Multiple Sclerosis

  24. Retrobulbar Optic neuropathy in Multiple Sclerosis in remission only with parenteral treatment

  25. Enzyme Immunoassay for Myelin Basic Protein in Cerebrospinal Fluid

  26. Value of Magnetic Resonance Imaging in assessing efficacy in clinical trials of Multiple Sclerosis therapies

  27. Clinical outcome measures & rating scales in Multiple Sclerosis trials

  28. High-Dose CorticoSteroids may prolong the Prothrombin time to dangerous levels in patients taking Warfarin

  29. Influenza Virus vaccination of patients with Multiple Sclerosis

  30. T-Cell to T-Cell activation in Multiple Sclerosis

  31. MRSI of Normal-Appearing White Matter in Multiple Sclerosis

  32. MRI measures & their relations with clinical disability in R/R & S/P Multiple Sclerosis

  33. The measurement of ambulatory impairment in Multiple Sclerosis

  34. Risk factors for developing Multiple Sclerosis after childhood Optic Neuritis

For additional Abstracts

Health Promotion Practices Of Women With Multiple Sclerosis

Stuifbergen AK, Roberts GJ
Arch Phys Med Rehabil 1997 Dec; 78(12 Suppl 5):S3-S9
Univ of Texas at Austin,
School of Nursing, 78701, USA
PMID# 9422001; UI# 98083919

To explore the health promotion behaviors of women with Multiple Sclerosis (MS), a chronic, disabling disease affecting the Central Nervous System.

Participants completed a battery of instruments measuring illness-related disability, health-promoting behaviors, and quality of life. Descriptive statistics were used to examine the frequency of various health promotion practices among women with MS.

Participants were grouped according to clinical course and compared on frequency of health-promoting behaviors using multivariate analysis of variance.

Path analysis was used to test the hypothesis that health-promoting behavior mediates the relation of illness severity to quality of life.

Participants & Outcome Measures
Women with physician-diagnosed MS (n = 629) who were community-residing were recruited with the assistance of two chapters of the National MS Society. Health Promoting Lifestyle Profile II; Quality of Life Index-MS Version.

Overall, these women scored lower on measures of physical activity (moderate effect size) and spiritual growth (small effect size) than the comparison "normative" sample.

Women with Benign Sensory and Relapsing/Remitting MS were more likely than women with progressive MS to engage in physical activity and spiritual growth behaviors. Health-promoting behaviors mediated the relation of illness-related disability to quality of life.

Findings highlight the impact of living with a chronic disabling condition on the frequency of health-promoting behaviors.

Additional research is needed to identify factors that enhance both the initiation and maintenance of health promotion behaviors.


    Medication Use During Pregnancy For Neurologic Conditions

Gilmore J, Pennell PB, Stern BJ
Neurol Clin 1998 Feb; 16(1): 189-206
Emory University, Assistant Professor of Neurology, Atlanta, Georgia
PMID# 9421548

Care of the pregnant patient is challenging because of the multiple physiologic changes associated with pregnancy and the need to consider the impact of any intervention on the fetus.

This article addresses management issues that arise while caring for patients with Epilepsy, Eclampsia, Stroke, Multiple Sclerosis, and Headache. An emphasis is placed on considerations involving medication use and approaches to patient care are suggested.


    Treatment Of AutoImmune Diseases Through Manipulation Of Antigen Presentation

Spack EG
Crit Rev Immunol 1997; 17(5-6): 529-536
Anergen, Inc., Dept of Immunology, Redwood City, CA 94063, USA
PMID# 9419440; UI# 98080710

In Rheumatoid Arthritis, HLA-DR alleles associated with elevated relative risk share a common sequence in the third hypervariable domain of the Major Histocompatibility Complex Class II molecule (MHC II).

Immunization of mice with a peptide vaccine comprised of the appropriate MHC II sequence in adjuvant blocked the onset and reduced the relapse rate of Experimental AutoImmune EncephaloMyelitis (EAE).

A phase I clinical trial testing a single injection of a third hypervariable domain peptide from the HLA-DRB1*0401 sequence in alum adjuvant showed that the vaccine is well tolerated and generates an anti-HLA-DR Antibody response in approximately 25% of the treated patients. A phase II trial testing multiple boosts is in progress.

In a more Antigen-specific approach, solubilized MHC II molecules loaded with an AutoAntigenic peptide are injected intravenously to induce unresponsiveness by the binding of the T-Cell receptor (TCR) in the absence of costimulation.

Appropriate soluble MHC II: AutoAntigenic peptide complexes inhibit the recall Antigen proliferative response of T clones or draining lymph node cells, and reduce the progression of EAE and Experimental AutoImmune Myasthenia Gravis (EAMG).

A test of a soluble HLA-DR2: Myelin Basic Protein (MBP) complex in Multiple Sclerosis is progressing in Phase I.


    T-Cell Receptor Peptides As Immunotherapy For AutoImmune Disease

Gold DP, Shroeder K, Golding A, Brostoff SW, Wilson DB
Crit Rev Immunol 1997; 17(5-6): 507-510
Sidney Kimmel Cancer Center, San Diego, CA 92121, USA
PMID# 9419437; UI# 98080707

The observations in both mouse and rat models of Experimental Allergic EncephaloMyelitis (EAE) demonstrating restricted T-Cell receptor (TCR) usage among Pathogenic T-Cells has led to the generation of a new class of therapeutic vaccines composed of TCR V region peptides.

Whether a similar approach will be of use in the treatment of human AutoImmune disorders is still unclear.

The experiments performed in our laboratory over the past several years have focused on two aspects of TCR peptide Immunoregulation, namely,

(1) how to identify the critical T-Cell populations involved in the pathology of AutoImmune Disease, and

(2) how to identify biologically relevant TCR peptides - those endogenous TCR peptides presented in association with MHC molocules on the surface of Pathogenic T-Cells that are recognized by Immunoregulatory T-Cell populations.

Results of our recently completed clinical studies regarding TCR V beta expression among CD4+ T-Cells in the Cerebral spinal fluid (CSF) of patients with Multiple Sclerosis suggests that these cells may be an appropriate T-Cell population to be targeted for TCR peptide therapy.

In addition, our studies on the Immune response to autologous, soluble TCR heterodimers may provide a strategy for the identification of new TCR peptide candidate vaccines.


    Initiation & Regulation of CNS AutoImmunity

Goverman J, Brabb T, Paez A, Harrington C, von Dassow P
Crit Rev Immunol 1997; 17(5-6): 469-480
Univ of Washington, Dept of Molecular Biotechnology, Seattle 98195, USA
PMID# 9419434; UI# 98080704

Our studies addressed the questions of how self-reactive T-Cells escape tolerance and what stimuli cause these T-Cells to initiate AutoImmune responses.

We employed Experimental Allergic EncephaloMyelitis (EAE) as an animal model of Multiple Sclerosis (MS).

Endogenous expression of myelin basic protein (MBP) iduces tolerance in T-Cells that recognize one region of MBP, whereas T-Cells specific for a different region escape tolerance.

Triggers of disease induction were investigated in a T-Cell receptor (TCR) transgenic model in which the majority of T-Cells recognize the MBP epitope that does not induce tolerance.

EAE occurs spontaneously in this model and the incidence of disease depends on microbial exposure.

EAE can also be actively induced by immunization with MBP peptide accompanied by injection of pertussis toxin as well as by administration of Pertussis Toxin alone.

Immunization with MBP peptide without Pertussis Toxin, however, stimulates the transgenic T-Cells, but the activated T-Cells do not accumulate in the Central Nervous System (CNS) or induce EAE.

Our studies suggest that initiation of AutoImmune Disease involves complex interactions between the NeuroEndocrine system as well as the Innate and Specific Immune Systems.


    Assessment Of Depression In Patients With Motor Neuron Disease & Other Neurologically Disabling Illnesses

Tedman BM, Young CA, Williams IR
J Neurol Sci 1997 Oct; 152 Suppl 1: S75-S79
The Walton Centre for Neurology and NeuroSurgery, Liverpool, UK
PMID# 9419059; UI# 98078868

Motor Neuron Disease (MND) is a severely disabling, relentlessly progressive neurological condition with a marked reduction in life expectancy which might be expected to be associated with significant Depression and psychological dysfunction following diagnosis.

There is very little data on the incidence of Depression in MND and most of the published evidence would suggest that depression is rare in patients with MND, especially when compared to other neurologically disabling illnesses.

We have studied 40 patients with MND and compared them to a group of 92 patients with Multiple Sclerosis (MS) attending a neurology clinic. Depression was assessed using the Beck Depression Index (BDI) and the Hospital Anxiety and Depression Scale (HAD).

There was no difference in incidence or severity of Depression in these two patient groups. For the whole study group there was no difference in Depression scores when compared by age, gender or marital status.

Depression scores showed a weak association with increasing physical disability measured by the SF36 Physical Function scale for the MS group but there was no association between Depression levels and SF36 physical function for the MND group.

The MND group did, however, show a significant association between Depression scores and pain measured by the SF36 scale.

Anxiety levels (HAD scale) were shown to be significantly higher in females and married (versus single, widowed or divorced) subjects for the group as a whole.

We conclude that Depression is at least as common in MND patients as other neurologically disabled patients with MS and may often be associated with significant pain.

Physicians and others involved in the care of patients with MND should be aware that depression and pain may be significant problems irrespective of the level of physical disability.


    Modulation Of T-Cell-Endothelial Adhesion By Astrocyte Conditioned Medium

Joseph J, Lublin FD, Knobler RL
Glia 1997 Dec; 21(4): 408-412
Dept ofNeurology, Jefferson Medical College, Philadelphia, Pennsylvania, USA
PMID# 9419016; UI# 98078825

Astrocytes and derived factors maintain the morphologic, phenotypic, and physiological properties of the Blood-Brain Barrier. Astroglial cells may also modulate Endothelial cell properties associated with the entry of inflammatory cells into the Brain.

The study of mechanisms of Lymphocyte migration through the Blood-Brain Barrier is critical to understanding the pathophysiology of AutoImmune (Multiple Sclerosis) and virus-induced Central Nervous System diseases (HIV-induced Dementia).

In this context the contribution of Astrocyte derived factors in regulating the interactions between inflammatory cells and Endothelial Cells of the Blood-Brain Barrier was studied.

The treatment of Endothelial cells derived from Brain or peripheral sources (Hepatic) with Astrocyte conditioned medium resulted in a dose dependent enhancement of adhesion of T-Cells to Endothelium.

The Antigen specificity of the T-Cells did not influence the findings. Identical results were obtained with fresh Concanavalin A activated T-Cells and T-Cell hybridomas generated using Myelin Basic Protein or chicken ovalbumin as Immunogens.

Further studies are in progress to define the active components in Astrocyte conditioned medium and Endothelial Cell Adhesion Molecules that are regulated in order to gain a better understanding of mechanisms of inflammatory cell entry into the Central Nervous System.


    Magnetic Resonance Spectroscopy Of Chronic Cerebral White Matter Lesions & Normal-Appearing White Matter In Multiple Sclerosis

Davie CA, Barker GJ, Thompson AJ, Tofts PS, McDonald WI, Miller DH
J Neurol NeuroSurg Psychiatry 1997 Dec; 63(6): 736-742
NMR Research Unit, Institute of Neurology, London, UK
PMID# 9416807

To test the hypothesis that irrecoverable Neurological deficit in Multiple Sclerosis is associated with Axonal Loss.

1H Magnetic Resonance Spectroscopy (MRS) was carried out in a group of patients with clinically definite Multiple Sclerosis (n=31).

Using this technique, the apparent concentration of NA ([NA] the sum of N-AcetylAspartate (NAA), a Neuronal marker, and N-AcetylAspartylglutamate has been compared in four groups of patients with Multiple Sclerosis classified as Relapsing/Remitting, Secondary/Progressive, Primary/Progressive, Benign, and a control group.

In the patients with Relapsing/Remitting disease (n=9) there was a highly significant reduction of apparent NA (median 8.73 mM, range 6.86 mM-10.74 mM, P=0.0008) from an area of high signal compared with the control group (median 11.97 mM, range 10.55 mM-14.5 mM).

In the patients with Secondary/Progressive disease (n=10), there was again a highly significant reduction of apparent NA (median 7.82 mM, range 3.5 mM-10.3 mM, P=0.0003) from an area of high signal compared with the control group.

In the patients with Primary/Progressive disease (n=6) there was once again a highly significant reduction of apparent NA (median 8.83 mM, range 6.95 mM-9.89 mM, P<0.002) from an area of high signal compared with the control group.

In the patients with Benign disease, however, there was no significant difference in the apparent NA (median 10.5 mM, range 8.53 mM-12.8 mM, P>0.05) from an area of high signal compared with the control group.

In the patients with Benign disease (n=5) there was also no significant difference in the apparent NA (median 10.74 mM, range 8.58 mM-13.4 mM, P>0.3) from an area of Normal-Appearing White Matter compared with the control group.

In the patients with Primary/Progressive disease, however, there was a significant reduction of apparent NA from an area of Normal-Appearing White Matter (median 8.78 mM, range 8.7 mM-12.38 mM, P< 0.025) compared with the control group.

There was a significant inverse correlation between [NA] from lesions in the patients with Multiple Sclerosis and disability as measured on the Kurtzke expanded disability scale score (r= -0.364, 0.05>P>0.02).

These findings support the hypothesis that Axonal loss is important in the development of disability in Multiple Sclerosis. They also provide evidence for Axonal loss in Normal-Appearing White Matter in patients with Primary/Progressive disease.


    Antiviral Immune Responses Modulate The Nature Of Central Nervous System (CNS) Disease In A Murine Model Of Multiple Sclerosis

Drescher KM, Pease LR, Rodriguez M
Immunol Rev 1997 Oct; 159: 177-193
Mayo Clinic/Foundation, Dept of Immunology, Rochester, Minnesota 55905, USA
PMID# 9416511; UI# 98078471

The spectrum of disease is influenced by factors related to both the Pathogen and the host, as well as the end points used in defining disease. In this article, the issue of disease resistance versus susceptibility will be examined in the framework that Genetic manipulation of either the Pathogen or the host Immune response alters the balance from disease protection towards PathoGenesis.

The response of the host may trigger both a protective and a Pathogenic Immune response. The failure to mount a protective immune response predisposes the Pathogen to persistence, which then becomes the target for Immunopathology.

This review will examine the factors involved both in virus-mediated PathoGenesis and in disease protection in the Theiler's model of human Multiple Sclerosis. By manipulating the character of the virus Pathogen and the specificity of the Immune response, the entire spectrum of human DeMyelinating disease is reproduced.


    The Infection Of Mouse By Theiler's Virus: From Genetics To Immunology

Monteyne P, Bureau JF, Brahic M
Immunol Rev 1997 Oct; 159: 163-176
Institut Pasteur, Unite des Virus Lents, CNRS, Paris, France
PMID# 9416510; UI# 98078470

Theiler's virus is a PicornaVirus of mouse which causes an acute EncephaloMyelitis followed by a persistent infection of the White Matter of the Spinal Cord with chronic Inflammation and DeMyelination.

This late disease is studied as a model for Multiple Sclerosis. Inbred strains of mice differ in their susceptibility to persistent infection and DeMyelination. Resistant strains clear the infection after the acute encephalomyelitis. This observation is the basis of Genetic studies which we used as a thread for this review.

The H-2D locus has a major effect on susceptibility. The H-2Db Gene is involved in a fast and intense CTL response which confers resistance. The Tcrb locus is also implicated, although there is no proof that the susceptibility Gene in this region codes for the T-Cell receptor.

A complete screen of the genome uncovered the role of the Ifng locus and led to the demonstration that IFN-gamma limits Viral spread in the White Matter. The roles of NK cells and B cells in limiting the infection are discussed. CD4+ T-Cells participate both in protection against the infection and in DeMyelination. Finally, the effect of non-immune factors in resistance is illustrated by mice with mutations in the MBP or PLP gene.


    A Replicated Prospective Investigation Of Life Stress, Coping, & Depressive Symptoms In Multiple Sclerosis

Aikens JE, Fischer JS, Namey M, Rudick RA
J Behav Med 1997 Oct; 20(5): 433-445
Mellen Center for Multiple Sclerosis Treatment and Research,
Cleveland Clinic Foundation, USA
PMID# 9415854; UI# 98077703

Life stress and coping responses jointly contribute to psychological adjustment in many chronic illness populations, but their significance in Multiple Sclerosis (MS) has not been extensively investigated.

Physical disability, cognitive status, negative life stress, coping strategies, and depressive symptoms were prospectively assessed in 27 adults with definite or probable MS. Of the original subjects, 22 provided two additional assessments at 6-month intervals.

After accounting for cognitive status and physical disability, life stress was positively correlated with current as well as future depressive symptoms; the prospective relationship was replicated within the second pair of prospective data waves. Escape avoidance was the only coping strategy that added to the prediction of future mood symptoms, but this was not replicated.

Results suggest that MS-related depressive symptoms are a function of prior disease-related impairment, life stress, and possibly escape avoidance coping.


    Managing Side-Effects Of Interferon-ß In Patients With Relapsing/Remitting Multiple Sclerosis

Munschauer FE 3rd, Kinkel RP
Clin Ther 1997 Sep; 19(5): 883-893
William C. Baird Multiple Sclerosis Research Center, State Univ of New York at Buffalo, USA
PMID# 9385477; UI# 98046587

In separate clinical trials, two preparations of recombinant Interferon (IFN)-ß, IFN ß-1a and IFN ß-1b, reduced exacerbation rates in Relapsing/Remitting Multiple Sclerosis (RR-MS).

Further, IFN ß-1a slows the progression of disability in patients with RR-MS. Although they are effective in the treatment of MS, use of these drugs is associated with both class-specific and agent-specific side effects.

Class-specific side effects include fever, chills, myalgias, arthralgias, and other flulike symptoms beginning 2 to 6 hours after injection and resolving within 24 hours of injection.

Transient worsening of pre-existing MS symptoms also occurs infrequently. Agent-specific side effects include injection-site reactions with IFN ß-1b.

Simple management strategies can be used to minimize these reactions, including patient education; tailoring the dose and time of administration of IFN-ß; and prescribing appropriate combinations of Acetaminophen, non-steroidal anti-inflammatory drugs, and Steroids.

Although side effects tend to diminish with treatment, successful management allows long-term administration of these drugs to achieve a reduction in disease activity and commensurate improvement in outcomes.


    Rationale For Early Treatment With Interferon-ß-1a in Relapsing/Remitting Multiple Sclerosis

Munschauer FE 3rd, Stuart WH
Clin Ther 1997 Sep; 19(5):868-882
William C. Baird Multiple Sclerosis Research Center,
School of Medicine and Biomedical Sciences,
State Univ of New York at Buffalo, USA
PMID# 9385476; UI# 98046586

Disease-modifying therapies are now available for the treatment of Relapsing/Remitting Multiple Sclerosis (RR-MS).

These drugs have transformed the management of RR-MS from simply treating symptomatic disease to providing effective but incomplete prophylaxis against further disease activity.

Our ability to modify disease activity is limited to reducing exacerbations and delaying progression of disability.

No intervention has yet been shown to reverse disability once it is established. To prevent disability, therapy should be initiated early in the course of the illness.

The rationale for early treatment is as follows:

(1) a high percentage of patients with clinically definite RR-MS progress from isolated attacks to neurologic impairment and then to disability within a short time;

(2) survival in MS is directly related to disability, so delaying the onset of disability could be expected to influence survival;

(3) Interferon (IFN) ß-1a has been shown to slow the progression of disability when given to RR-MS patients with impairment or mild disability; and

(4) Magnetic Resonance Imaging studies indicate that MS patients frequently have evidence of Central Nervous System inflammation without overt clinical symptoms, and it has been postulated that treatment of subclinical disease as identified by Magnetic Resonance Imaging may improve long-term outcome.

IFN-ß reduces the number of new T2-weighted lesions, as well as the number and volume of gadolinium-enhanced lesions.

Aggressive early treatment with IFN ß-1a is recommended, particularly for patients with risk factors suggesting an unfavorable prognosis.


    Mood Disturbance Versus Other Symptoms of Depression In Multiple Sclerosis

Nyenhuis DL, Rao SM, Zajecka JM, Luchetta T, Bernardin L, Garron DC
J Int Neuropsychol Soc 1995 May; 1(3): 291-296
Rush-Presbyterian-St. Luke's Medical Center, Dept of Psychology and Social Sciences, Chicago, IL 60612, USA
PMID# 9375223; UI# 98042793

We administered the Multiscale Depression Inventory (MDI) and the Beck Depression Inventory (BDI) to 84 Multiple Sclerosis (MS) patients, 101 patients diagnosed with major Depression and 87 nonmedical, nonpsychiatric controls.

The MDI consists of three separate Depression scales measuring Mood, vegetative, and evaluative symptoms.

    We found that:
  • MS patients did not significantly differ from the controls in mood symptoms,
  • the Depression prevalence rate in MS patients was significantly lower when measured by the Mood scale (17.7%) than by the BDI (30.5%) or MDI total score (26.6%), and
  • MS patients showed significantly less Mood disturbance than a non-MS comparison group matched on BDI measured Depression severity.

We suggest that the inclusion of non-Mood symptoms in self-report Depression scales may artificially raise both prevalence rates and severity ratings of MS related Depression and that the most valid measure of Depression in MS is Mood disturbance.


    Problem Solving By Patients With Multiple Sclerosis: Comparison Of Performance On The Wisconsin & California Card Sorting Test

Beatty WW, Monson N
J Int Neuropsychol Soc 1996 Mar; 2(2): 134-140
Dept ofPsychiatry and Behavioral Sciences,
Univ of Oklahoma Health Sciences Center, Oklahoma City 73190, USA
PMID# 9375198

Problem solving by patients with clinically definite Multiple Sclerosis (MS) was examined using the Wisconsin and California Card Sorting Tests (WCST and CCST).

On the WCST, the MS patients achieved fewer categories and made more perseverative responses and errors than controls, confirming results of several previous studies.

On the CCST, the MS patients generated and identified fewer concepts, but they performed normally when sorting was cued by the experimenter and they made no more perseverations than controls.

Although findings from the WCST indicate that the problem solving deficits by MS patients closely resemble those exhibited by patients with various conditions that produce frontal lobe dysfunction.

Results from the CCST indicate that the problem solving difficulties exhibited by patients with MS are distinct and probably represent a primary deficit in concept formation.


    Isolated Cranial Nerve Palsies In Multiple Sclerosis

Thomke F, Lensch E, Ringel K, Hopf HC
J Neurol NeuroSurg Psychiatry 1997 Nov; 63(5):682-685
Univ of Mainz, Dept of Neurology, Germany
PMID# 9408116; UI# 98070054

During a 10 year period 24 patients with definite Multiple Sclerosis with isolated Cranial Nerve Palsies were studied (Third and Fourth Nerve: one patient each, Sixth Nerve: 12 patients, Seventh Nerve: three patients, Eighth Nerve: seven patients), in whom Cranial Nerve Palsies were the presenting sign in 14 and the only clinical sign of an exacerbation in 10 patients.

MRI was carried out in 20 patients and substantiated corresponding BrainStem lesions in seven patients (Third Nerve: one patient, Sixth Nerve: four patients, Eighth Nerve: two patients).

Additional abnormal findings of Electro-Oculography, or Masseter Reflex, or Blink Reflex, or combinations of these were found in 20 patients and interpreted in favor of a BrainStem lesion at the level of the respective Cranial Nerve.

In 11 of 14 patients with isolated Cranial Nerve Palsies as the presenting sign of Multiple Sclerosis, dissemination in space was documented by MRI, and in the remaining three by Evoked Potentials.

In patients with Multiple Sclerosis with isolated Cranial Nerve Palsies, MRI is the most sensitive method of documenting dissemination in space and ElectroPhysiological testing the most sensitive at disclosing BrainStem lesions.


    Age At Immigration To England Of Asian & Caribbean Immigrants & The Risk Of Developing Multiple Sclerosis

Dean G, Elian M
J Neurol NeuroSurg Psychiatry 1997 Nov; 63(5): 565-568
The Medico-Social Research Board, Dublin, Ireland
PMID# 9408093; UI# 98070031

Previous studies have shown that Multiple Sclerosis is very uncommon among Indian and Pakistani immigrants to England but that their children born in the United Kingdom, in the age groups available for study, have a similar risk of developing the disease as occurs in the general British population.

The present study was to ascertain if these immigrants who enter England as children below the age of 15, have a higher risk of developing Multiple Sclerosis than those that enter after this age.

A search was made in Greater London, the West Midlands, Leicester, Bradford, Halifax, and Huddersfield to find ethnic Indian, Pakistani, and Bangladeshi immigrants to England with Multiple Sclerosis.

During the course of the study some immigrants from the Caribbean with Multiple Sclerosis were also found.

The population at risk by ethnic group and age at entry was not available from the 1991 Census but was available in the annual Labour Force Surveys.

Indian and Pakistani immigrants who entered England younger than 15 had a higher risk of developing Multiple Sclerosis than those that entered after this age.

Caribbean immigrants, who have a higher Multiple Sclerosis prevalence than Asian immigrants, did not show this difference.

This study confirms previous studies which show that the environment during childhood is a major factor in determining the risk of developing Multiple Sclerosis.


    The Detection Of Intrathecal Synthesis Of Anti-Herpes Simplex IgG AntiBodies: Comparison Between An Antigen-Mediated Immunoblotting Technique & Antibody Index Calculations. European Union Concerted Action On Virus Meningitis & Encephalitis

Monteyne P, Albert F, Weissbrich B, Zardini E, Ciardi M, Cleator GM, Sindic CJ
J Med Virol 1997 Dec; 53(4): 324-331
Catholic Univ of Louvain, Laboratory of NeuroChemistry, Brussels, Belgium
PMID# 9407379; UI# 98071270

The detection of Intrathecal antibody synthesis was compared by the calculation of antibody indices (AI) derived from ELISA techniques with the detection of virus-specific oligoclonal IgGs by an Antigen-mediated capillary blot technique.

Twenty-seven paired Serum and CerebroSpinal Fluid (CSF) samples were examined from 15 Immuno-competent patients with Herpes Simplex Virus Encephalitis (HSE) diagnosed by PCR on early CSF samples.

These techniques were also applied to paired samples from 20 Multiple Sclerosis (MS) patients, 10 patients with other inflammatory neurological diseases and 10 patients with non inflammatory neurological disorders.

There was a good correlation between the results obtained by AI and those obtained by Immunoblotting, especially in HSE (2 discordant results out of 27).

Discrepancies were more frequent (25%) in MS patients where a "polyspecific" reaction characterized by low affinity AntiBodies is known to occur.

Some of the discrepancies could, in part, be due to serological cross-reaction with Varicella Zoster Virus.


    Dystonia As An Isolated Symptom of Multiple Sclerosis?

Azzimondi G, Rinaldi R, Liguori R, Tonon C, Martini E, D'Alessandro
Ital J Neurol Sci 1997 Oct; 18(5): 301-302
Servizio di Neurologia, Policlinico S. Orsola Malpighi, Bologna, Italy
PMID# 9412856; UI# 98074336

Sustained Dystonia has seldom been reported during the course of Multiple Sclerosis (MS) [5-8, 10], and has been described as the first manifestation of the disease in only three cases [1,3]. We describe a patient with a diagnosis of laboratory-supported, defined MS in which sustained Dystonia was the only neurological symptom.


    Pudendal Nerve Somatosensory Evoked Potentials In Probable Multiple Sclerosis

Sau GF, Aiello I, Siracusano S, Belgrano M, Pastorino M, Balsamo P, Magnano I, Rosati G
Ital J Neurol Sci 1997 Oct; 18(5):289-291
Universita di Sassari, Clinica Neurologica, Italy
PMID# 9412853; UI# 98074333

Bladder dysfunctions are often observed in patients with Multiple Sclerosis (MS).

In order to evaluate their sensitivity in detecting abnormalities in Bladder central control pathways, Pudendal Nerve Somatosensory Evoked Potentials (pSEPs) were recorded in 16 patients with clinically probable MS: six were affected by retention or urge incontinence, and ten were asymptomatic.

Conventional Visual, Auditory and Somatosensory Evoked Potentials were also recorded, and all of the patients underwent a Urodynamic examination.

Prolonged latency or the absence of pSEP Cortical responses was found in eight of the ten asymptomatic patients, and in all of the symptomatic cases (87.5%).

The Urodynamic evaluation revealed abnormalities in 12 patients (75%). Our findings seem to indicate an early and frequent involvement of Bladder control pathways in MS patients, as well as a high rate of subclinical disorders.


    Neurologic Changes In Patients With Multiple Sclerosis

[Article in Spanish]

Arlandis Guzman S, Sanz Chinesta S, Burguera Hernandez JA, Martinez Agullo E
Arch Esp Urol 1997 Jul; 50(6): 680-686
Hospital Universitario La Fe, Servicio de Urologia, Valencia, Espana
PMID# 9412370; UI# 97415996

To evaluate the presence of Urinary symptoms in 77 patients with Multiple Sclerosis.

The neurological compromize and the degree of functional disability were evaluated through the Minimum Dossier of Disability for Multiple Sclerosis.

The pertinent data for the Urinary symptoms were collected through a directed survey. A Urodynamic study was performed to evaluate Bladder function.

81.8% of the patients had Urinary symptoms, the most prevalent being the mixed syndrome (52%). Neurological involvement and functional disability were greater in the male patients and there was a higher incidence of Urinary symptoms (91%).

Urgency (66.6%), frequency (60.3%) and Dysuria (53.8%) were the most common Urinary symptoms.

The complication rate was low; infection was the most common complication (14.28%) and was more prevalent in the females. Detrusor hyperreflexia (60%) was the most frequent Urodynamic finding.

Urinary symptoms are frequent in Multiple Sclerosis (81.8%), the most prevalent being the mixed syndrome.

Neurological involvement and functional disability are greater in the male patients and there is a higher incidence of Urinary symptoms.

There is a significant correlation between the severity of neurological compromize (Pyramidal and Cerebellar) and the degree of functional disability and the presence of Urinary symptoms.


    Fast Spin Echo & Fast Fluid Attenuated Inversion Recovery Sequences In Multiple Sclerosis

[Article in Italian]

Paolillo A, Giugni E, Bozzao A, Bastianello S
Radiol Med (Torino) 1997 Jun; 93(6): 686-691
Universita, La Sapienza, Dipartimento di Scienze Neurologiche, Roma
PMID# 9411514; UI# 98001138

Fast Spin Echo (FSE) and fast Fluid Attenuated Inversion Recovery (fast-FLAIR) MR sequences were compared with Conventional Spin Echo (CSE) in quantitating Multiple Sclerosis (MS) lesion burden.

For each sequence, the total number and volume of MS lesions were calculated in 38 Remitting MS patients using a semiautomated lesion detection program.

CSE, FSE and fast-FLAIR images were reported on randomly and at different times by two expert observers. Interobserver differences, the time needed to quantitate MS lesions and lesion signal intensity (contrast-to-noise ratio and overall contrast) were considered.

    The lesions were classified by site into
  • Infratentorial
  • White Matter
  • Cortical/SubCortical

A total of 2970 lesions with a volume of 961.7 cm3 was calculated on CSE images. FSE images depicted fewer (16.6%; p < .005) and smaller (24.9%; p < .0001) lesions and the differences were statistically significant.

Despite an overall non-significant reduction for fast-FLAIR images (.5% and 4.8% for lesion number and volume, respectively), significantly lower values (lesion number: p < .01; volume: p < .04) were observed for InfraTentorial lesions, while significantly higher values were seen for Cortical/SubCortical lesions (lesion number: p < .01; volume: p < .02).

A higher lesion/White Matter contrast (p < .002), a significant time saving for lesion burden quantitation (p < .05) and very low inter-observer variability were found in favor of fast-FLAIR.

Our data suggest that, despite the limitations regarding InfraTentorial lesions, fast-FLAIR sequences are indicated in MS studies because of their good identification of Cortical/SubCortical lesions, almost complete inter-observer agreement, higher contrast-to-noise ratio and the limited time needed for semi-automated quantitation.


    Diagnostic Importance Of Middle Latency Auditory Evoked Potentials (MLAEP) In Multiple Sclerosis

[Article in French]

Delalande I, Thomas D, Forzy G, Hautecoeur P, Gallois P
NeuroPhysiol Clin 1997 Sep; 27(4): 293-299
Hopital Saint-Philibert, Service De Neurologie, Lomme, France
PMID# 9411208; UI# 98010992

This study was aimed at assessing the interest of Middle Latency Auditory Evoked Potentials (MLAEP) recordings in Multiple Sclerosis (MS).

BrainStem Auditory Evoked Potentials (BAEP) and MLAEP were recorded in 40 control subjects and 65 patients who had MS according to Poser's criteria.

Na and Pa latencies were significantly delayed in the MS group. These abnormalities were detected in 60% of the patients.

In 26% of the cases with normal BAEP, abnormalities of MLAEP were present. In 71% of the patients abnormalities of both BAEP and MLAEP were observed.

These results suggest the ability of MLAEP recordings to detect lesions of the Auditory Pathways Rostral to the Pons and show the value of their combined recordings in MS patients.


    Retrobulbar Optic Neuropathy In Multiple Sclerosis In Remission Only With Parenteral Treatment

[Article in Romanian]

Constantin C, Anghel K, Romanescu C
Oftalmologia 1997; 41(4): 350-352
Clinica II Oftalmologie Iasi
PMID# 9409992; UI# 98027489

The authors are presenting a case diagnosed with Retrobulbar Neuritis in the left eye secondary to Multiple Sclerosis. The symptoms submitted only under infusions with CorticoSteroids.

Despite the lack of MethylPrednisolone, Hydrocortisone was used successfully. This case supports the efficiency of intravenous treatment of Optic Neuritis as modern therapy in Neuro-Ophthalmology.


    Enzyme Immunoassay For Myelin Basic Protein In CerebroSpinal Fluid

Najeme F, Julien J, Herblot S, Dousset V, Brochet B, Bonnet J
Brain Res Brain Res Protoc 1997 May; 1(2): 133-138
Laboratoire d'Immunologie Moleculaire, Batiment 1b-Carreire Nord,
Universite de Bordeaux II, France
PMID# 9385076; UI# 98040224

Myelin Basic Proteins (MBPs) are a set of proteins making up about 30% of the protein content of the Central Nervous System Myelin. Four human isoforms have been identified. The most abundant is a highly conserved 18.5 kDa polypeptide.

For this species, the Amino Acid sequence homologies between human and monkey or human and chick are 98.2% and 71.1%, respectively.

As a consequence, there is a very good Immunological cross-reactivity between the mammalian MBP. This protein has been extensively used to induce Experimental Allergic Encephalomyelits (EAE) in numerous animals.

The evolution of chronic EAE in animal is similar to that of Multiple Sclerosis (MS), a DeMyelinating human pathology, and chronic EAE is considered to be an animal model of MS.

In DeMyelinating pathologies, MBP concentration in the CerebroSpinal Fluid (CSF) is considered to be a good marker of DeMyelination. MBP concentration, in biological fluids, is generally determined by radioImmunoassay (RIA).

The RIA technique currently used is highly sensitive (0.1-2.5 ng/ml) but has the drawback of requiring the handling of radioactivity and frequent labelling of MBP.

So we developed a new enzyme Immunoassay (EIA) technique. Our technique has the same sensitivity as RIA, needs only small volumes of CSF (50 microliters) and the enzyme-labelled MBP tracer is stable for at least 12 months.


    Value Of Magnetic Resonance Imaging In Assessing Efficacy In Clinical Trials Of Multiple Sclerosis Therapies

Erickson BJ, Noseworthy JH
Mayo Clin Proc 1997 Nov; 72(11): 1080-1089
Mayo Clinic, Dept of Diagnostic Radiology, Rochester, Minnesota 55905, USA
PMID# 9374985; UI# 98042418

Magnetic Resonance Imaging (MRI) has become an important technique for monitoring the effectiveness of putative treatments for Multiple Sclerosis (MS) because of its high sensitivity, objectivity, and noninvasive nature.

Its importance as a surrogate measure of disease, however, is an issue that is more difficult to validate than might seem to be the case.

In this review, we describe the role of MRI in the assessment of putative therapies for MS. New magnetic resonance techniques and methods of image analyzes aimed at better demonstrating the nature and extent of disease are discussed, and the role of MRI in published MS therapeutic trials is examined.

MRI is a frequently used secondary outcome measure for putative treatment strategies for MS. Although it is sensitive to changes in the inflammatory component of the MS disease process, poor correlation has been noted between MRI findings and long-term patient outcome.

There is a widespread expectation that new Magnetic Resonance techniques - such as Fluid Attenuated Inversion Recovery, Magnetization Transfer Imaging, and Magnetic Resonance Spectroscopy - will ultimately be useful for characterization of pathologic changes within the MS lesion and more generally of the MS disease process.

Whether Magnetic Resonance changes seen in experimental therapies predict the long-term clinical course of the disease remains to be determined.


    Clinical Outcome Measures & Rating Scales In Multiple Sclerosis Trials

Wingerchuk DM, Noseworthy JH, Weinshenker BG
Mayo Clin Proc 1997 Nov; 72(11): 1070-1079
Mayo Clinic Rochester, Dept of Neurology, Minnesota 55905, USA
PMID# 9374984; UI# 98042417

In this review, we analyzed clinical outcome measures used in Multiple Sclerosis (MS) clinical trials in which the primary goal is to slow or arrest progression of disease.

In addition, we examined rating scales that quantify symptomatic complications of MS (for example, Spasticity) and the current role of Magnetic Resonance Imaging in MS treatment trials.

Each proposed scale has advantages and deficiencies, and none meets all the criteria for an ideal outcome measure.

The validity of trial design may be improved by using combinations of selected components of current scales as well as new instruments targeted to specific variables (such as motor strength). Symptom-specific rating scales are most appropriately used in trials of symptomatic therapeutic strategies for MS.

Until serial Magnetic Resonance Imaging changes are definitely known to predict long-term impairment and disability in patients with MS, clinical outcome measures will remain the primary means of assessing therapeutic efficacy in phase III clinical trials.


    Treatment Of Multiple Sclerosis With High-Dose CorticoSteroids May Prolong The Prothrombin Time To Dangerous Levels In Patients Taking Warfarin

Kaufman M
Mult Scler 1997 Aug; 3(4):248-249
Carolinas Medical Center, Multiple Sclerosis Center, Charlotte, North Carolina 28232, USA
PMID# 9372508; UI# 98039777

Two patients who were taking Warfarin experienced significant prolongations of the prothrombin time (protime) after treatment with high-dose CorticoSteroids for rapid progression of MS. This complication of therapy is potentially life-threatening.


    Influenza Virus Vaccination Of Patients With Multiple Sclerosis

Mokhtarian F, Shirazian D, Morgante L, Miller A, Grob D, Lichstein E
Mult Scler 1997 Aug; 3(4):243-247
SUNY Health Science Center/Maimonides Medical Center, Dept of Medicine, Brooklyn 11219, USA
PMID# 9372507; UI# 98039776

Prior to vaccination with a trivalent influenza vaccine (AT/Texas, AB/Beijing, and BP/Panama), Sera from 19 MS patients had a significantly higher mean level of antibody than 9 normal subjects to AT strain of influenza, but not to AB or BP strains.

After Flu vaccination, the mean anti-AT and anti-AB antibody titers significantly increased 4-fold in 11 MS patients and 9 normal subjects. The ratio of MS responders (6/11), however, was lower than normal (8/9).

The mean PBL proliferative response to the Flu Antigens increased after vaccination significantly more in MS patients than in normal subjects, and increased in 9 of 11 MS patients and 3 of 9 normal subjects.

Although MS patients responded to Flu Antigens with higher antibody levels and proliferative responses of PBL, than normal subjects, a clinical protective effect of the vaccine against Flu was not clearly demonstrated in these patients, and vaccination did not cause or protect against exacerbation of MS.


    T-Cell To T-Cell Activation In Multiple Sclerosis

Lindsey JW, Kerman RH, Wolinsky JS
Mult Scler 1997 Aug;3(4):238-242
Univ of Texas-Houston Medical School, Dept of Neurology, USA 77030
PMID# 9372506; UI# 98039775

Activated T-Cells are able to stimulate proliferation in resting T-Cells through an Antigen non-specific mechanism. The in vivo usefulness of this T-Cell to T-Cell activation is unclear, but it may serve to amplify Immune responses.

T-Cell to T-Cell activation could be involved in the well-documented occurrence of Multiple Sclerosis (MS) exacerbations following Viral infections. Excessive activation via this pathway could also be a factor in the etiology of MS.

We tested the hypothesis that excessive T-Cell to T-Cell activation occurs in MS patients using in vitro proliferation assays comparing T-Cells from MS patients to T-Cells from controls.

When tested as responder cells, T-Cells from MS patients proliferated slightly less after stimulation with previously activated cells than T-Cells from controls.

When tested as stimulator cells, activated cells from MS patients stimulated slightly more non-specific proliferation than activated cells from controls.

Neither of these differences were statistically significant. We conclude that T-Cell proliferation in response to activated T-Cells is similar in MS and controls.


    MRSI Of Normal-Appearing White Matter In Multiple Sclerosis

Rooney WD, Goodkin DE, Schuff N, Meyerhoff DJ, Norman D, Weiner MW
Mult Scler 1997 Aug;3(4):231-237
Univ of California, Dept of Radiology, San Francisco, USA
PMID# 9372505; UI# 98039774

The primary goal of this study was to determine if differences in proton magnetic resonance spectroscopy signals exist between Normal-Appearing White Matter (NAWM) of Multiple Sclerosis (MS) patients and White Matter of control subjects.

Water suppressed proton Magnetic Resonance Spectroscopic Imaging was used to determine the signal intensities of N-acetylated moieties (NA, predominantly N-AcetylAspartate (NAA) the putative Neuronal marker), Creatine and Phosphocreatine (Cr), and Cholines (Ch) in 19 MS patients (15 Relapsing/Remitting and four Secondary/Progressive) and 19 age matched control subjects.

NA/Cr was significantly reduced (P < 0.001) in MS NAWM (1.8 +/- 0.2; x +/- s.d.) distant from MRI detected lesion areas compared to White Matter of control subjects (2.1 +/- 0.2). This reduction was due to an increase in Cr from 0.39 +/- 0.04 (arbitrary units) in controls to 0.45 +/- 0.05 in MS patients.

There was no significant change in NA or Ch in MS NAWM compared to controls. NA/Cr, distant from MRI lesion, was negatively correlated with total Brain lesion volume as measured from T2-weighted MRI. We interpret the reduced NA/Cr in MS NAWM to indicate diffuse microscopic disease.


    MRI Measures & Their Relations With Clinical Disability In Relapsing/Remitting & Secondary/Progressive Multiple Sclerosis

Giugni E, Pozzilli C, Bastianello S, Gasperini C, Paolillo A, Koudriavtseva T, Frontoni M, Farina D, Bozzao L
Mult Scler 1997 Aug;3(4):221-225
UnivLa Sapienza of RomeDept of Neurological Sciences, PMID# 9372503; UI# 98039772

To further evaluate the relationship between clinical disability and Magnetic Resonance Imaging (MRI) lesion burden, we examined 85 patients with Clinically Definite Multiple Sclerosis (54 Relapsing/Remitting and 31 Secondary/Progressive).

This cross-sectional study reports on the correlations between total and InfraTentorial lesion volume on both T1 and T2 weighted images, and overall physical disability measured by Expanded Disability Status Scale, ambulation index and individual functional systems.

Assessment of the HypoIntense lesion load on T1 weighted images rather than the HyperIntense lesion load on T2 weighted images at Brain MRI was shown to be useful for differentiating Relapsing/Remitting from Secondary/Progressive Multiple Sclerosis.

A weak relationship between disability and total lesion volume on both T1 and T2 weighted images was found in Relapsing/Remitting Multiple Sclerosis.

In Secondary/Progressive Multiple Sclerosis, InfraTentorial lesion volume on T2 weighted images represents the only marker of disability.

Finally, the presence of Cerebellar, BrainStem and Mental impairment was significantly associated to a greater total lesion volume on MRI, while no relationship was found with other functional systems.


    The Measurement Of Ambulatory Impairment In Multiple Sclerosis

Schwid SR, Goodman AD, Mattson DH, Mihai C, Donohoe KM, Petrie MD, Scheid EA, Dudman JT, McDermott MP
Neurology 1997 Nov;49(5):1419-1424
Univ of Rochester Medical Center, Dept of Neurology, Rochester, NY, USA
PMID# 9371932; UI# 98039201

The objective of this study was to examine the relationships between continuous measures of ambulatory impairment in MS patients and their ordinal counterparts. Much of the disability caused by MS is due to ambulatory impairment.

The Expanded Disability Severity Scale (EDSS) and the Ambulation Index (AI) are ordinal measures of MS severity based largely on the maximal distance subjects can walk (Dmax) and the time to walk 8 m (T8), respectively.

At EDSS levels 6.0 to 7.0 and AI levels 3 to 6, scores are defined more by the use of ambulatory aids, rather than by Dmax or T8. We determined Dmax (up to 500 m), T8, the EDSS score, and the AI in 237 ambulatory MS patients.

The maximal distance subjects could walk and T8 were strongly related to their ordinal counterparts (Spearman r = 0.65 and 0.91, respectively), but the continuous measures showed considerable variability within EDSS and AI levels that the ordinal scales did not reflect.

Most of the variability occurred at EDSS levels 6.0 to 7.0 and AI levels 3 to 6.

Because the use of an aid did not clearly predict Dmax or T8, many patients in these ranges had better ambulatory function based on the continuous measures than those with less disability according to the ordinal scales.

We found that Dmax and T8 provide more precise information about ambulatory impairment in MS than do the EDSS and AI, allowing better discrimination of differences between patients and potentially greater sensitivity to detect therapeutic effects in clinical trials.


    Risk Factors For Developing Multiple Sclerosis After Childhood Optic Neuritis

Lucchinetti CF, Kiers L, O'Duffy A, Gomez MR, Cross S, Leavitt JA, O'Brien P, Rodriguez M
Neurology 1997 Nov; 49(5):1413-1418
Mayo Clinic, Dept of Neurology, Rochester, MN, USA
PMID# 9371931; UI# 98039200

We reviewed the records of all children (younger than 16 years of age) who presented with a diagnosis of Optic Neuritis (ON) identified through the comprehensive records-linkage system at the Mayo Clinic and identified 94 cases between 1950 and 1988 with a documented history of idiopathic ON.

Detailed follow-up information was available on 79 patients, with a median length of follow-up of 19.4 years.

Life-table analysis showed that 13% of the 79 patients with isolated ON had progressed to clinically or laboratory-supported definite Multiple Sclerosis (MS) by 10 years of follow-up, 19% by 20 years, 22% by 30 years, and 26% by 40 years.

Gender, age, funduscopic findings, Visual Acuity, or family history of either ON or MS did not predict the development of MS.

The presence of bilateral sequential or recurrent ON increased the risk of developing MS (p = 0.002; hazard ratio = 5.09), whereas the presence of infection within 2 weeks before the onset of ON decreased the risk of developing MS (p = 0.060; hazard ratio = 0.24).

This study of childhood ON supports the lower risk of recurrence and progression to MS compared with adults.

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