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
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
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
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- 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
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.