Depression and multiple sclerosis

The objective of the present study were (1) to ascertain the lifetime risk of a depression in a representative group of multiple sclerosis (MS) patients, (2) to assess the morbidity risks for depression among first-degree relatives of these MS patients, and (3) to compare these familial risks for first-degree relatives of MS patients with those for first-degree relatives of a primary depression population, i.e., depression but no MS. We psychiatrically evaluated 221 MS patients (index cases) using a structured clinical interview for the DSM-III-R and calculated the rate and lifetime risk of depression for these index cases using the product limit estimate of survival function. We obtained psychiatric histories for all first-degree relatives of index cases, and we calculated morbidity risks for depression for these relatives using the maximum likelihood approach and compared the risks using the likelihood ratio tests. Index cases had a 50.3% lifetime risk of depression. Morbidity risks for depression among first-degree relatives of index cases were decidedly lower when compared with morbidity risks among first-degree relatives of the reference population. Although there appears to be a very high rate of depression among MS patients, the data for their first-degree relatives do not support a clear genetic basis for this depression, or at least the same genetic basis that probably operates within families when depression occurs in the absence of MS.     

Pregnancy and multiple sclerosis

In this review, we summarize the available information on the short- and long-term effects of pregnancy on the course of multiple sclerosis (MS). Published studies that used established criteria for the diagnosis of MS were given more weight than studies in which the criteria for diagnosis were unstated or unclear. Population-based studies were emphasized more than clinic-based studies, unless the clinic base was well defined and thought to be reasonably representative of the MS population in the geographic area. For completeness, small studies were also included but weighted accordingly in our overall conclusions. Methodologic limitations and biases inherent in the study methods are discussed. We conclude that patients with relapsing MS have an increased risk of relapse during the initial 6-month postpartum period. This increased risk does not seem to have a detrimental effect on the rate of developing sustained disability. In fact, a full-term pregnancy may increase the time interval to reaching a common disability endpoint-walking with the aid of a cane or crutch--or to having a secondarily progressive course. Evidence indicates that pregnancy may alter T-lymphocyte functions and cause clinically relevant consequences. The specific biochemical mechanisms responsible for these observations, however, remain undefined. Because of limitations of current knowledge, our conclusions are tentative at best. The data are most applicable to patients with relapsing-remitting MS in its early stages. MS is an unpredictable disease and is only one of many factors that patients must consider when a pregnancy is contemplated.     

Genetics of multiple sclerosis

The cause of MS is unknown. There is considerable circumstantial evidence that MS is a complex trait, probably autoimmune in nature, and is determined by both genetic and environmental factors. At present, it must be acknowledged, however, that our understanding of the pathogenesis of MS is minimal. Very little is known about the genes determining disease susceptibility and perhaps even less is understood about environmental factors that influence penetrance or the geographic distribution. This lack of knowledge results neither from lack of effort nor from a shortage of fertile imaginations. Almost every imaginable hypothesis has, in the past, found some support. The intractability of the problem could well result from its complexity, because answers to testable hypotheses are commonly negative or ambiguous. Today, the opportunity exists for researchers to provide such answers because of recent major developments. The first development is the recognition that MS research requires a relatively large pool of well-ascertained, carefully diagnosed, and longitudinally well-characterized MS patients. The last two developments are the identification and successful application of statistical and molecular genetic techniques carrying sufficient power to allow the exploration of complex traits such as MS.     

Neuroimaging in multiple sclerosis

Neuroimaging in multiple sclerosis is now dominated by MR imaging. This article will focus primarily on conventional MR imaging studies in multiple sclerosis, but will also discuss briefly some of the more recent advances related to MR imaging. Fast spin-echo imaging, fluid attenuated inversion recovery MR studies, three-dimensional volumetric studies, magnetization transfer, and magnetic resonance spectroscopy as it applies to multiple sclerosis are examined.     

Prognosis in multiple sclerosis

Prognosis of the natural course of multiple sclerosis is most often measured on Kurtzke's "expanded disability status scale" (EDSS), a non-linear scale over 20 steps, heavily weighted on mobility. Optic neuritis and sensory disturbances as initial symptoms, lower age at onset of the disease, female sex and a longer interval between relapses are indicators of a more favorable prognosis. As a rule, disability as measured on this scale 5 years after onset corresponds to 3/4 of the disability status after 15 years. The number of relapses diminishes naturally over the course of the disease. Presence and extent of lesions on the initial MRI of the brain in clinically isolated syndromes are valuable predictors of dissemination of the disease process over the following 5-10 years. New therapies (e.g. interferon beta 1b and 1a, copolymer 1) reduce relapse frequency by 1/3 and diminish the extent of pathological lesions in brain MRI, but fail to show (as yet) significant influence on disability.     

Bioelectromagnetic applications for multiple sclerosis

There are EM effects on biology that are potentially both harmful and beneficial. We have reviewed applications of EM fields that are relevant to MS. It is possible that EM fields could be developed into a reproducible therapy for both symptom management and long-term care for MS. The long-term care for MS would have to include beneficial changes in the immune system and in nerve regeneration.     

Interferon beta for multiple sclerosis

OBJECTIVE: To introduce readers to the use of a new agent, interferon beta-1b (IFN beta ser), in the treatment of relapsing-remitting multiple sclerosis (RRMS). Therapeutic and economic issues surrounding IFN beta ser are discussed, as are its pharmacology, clinical efficacy, adverse effects, and dosage guidelines. DATA SOURCES: A MEDLINE search was used to identify pertinent literature, including clinical trials and reviews. STUDY SELECTIONS: All available trials were reviewed. DATA EXTRACTION: Since trials evaluating subcutaneously administered interferon beta are sparse, clinical trials evaluating intrathecal IFN beta ser were included, as was toxicology information from the oncology population. DATA SYNTHESIS: IFN beta ser has recently been approved by the Food and Drug Administration for the treatment of RRMS. Its exact mechanism of action is unknown, but it may downregulate interferon gamma (IFN gamma) production and the IFN gamma-stimulated major histocompatibility complex antigen expression, and/or augment T-suppressor cell function. Primary adverse effects include flu-like symptoms, fever, chills, myalgia, sweating, and injection-site reactions. Clinical efficacy has been investigated in 372 ambulatory patients with RRMS. IFN beta ser treatment resulted in a reduction in the annual exacerbation rate and a greater proportion of exacerbation-free patients. Burden of central nervous system disease was also significantly reduced in treated patients. However, no reductions were detected on the Scripps Neurologic Rating Scale or with confirmed endpoint scores on the Kurtzke Expanded Disability Status Scale. Although many questions remain concerning IFN beta ser's long-term efficacy, its benefits in patients with other types of multiple sclerosis (MS), and its effect on progression of disease and ultimate disability, IFN beta ser is the first treatment modality that has substantially altered the natural course of MS in a controlled clinical trial. CONCLUSIONS: IFN beta ser is not a cure for MS, but it is well tolerated and patients with RRMS have shown significant improvements in exacerbation rates and burden of central nervous system disease. IFN beta ser should be considered a definite improvement in RRMS treatment, although many therapeutic issues remain unanswered. Additional clinical trials are needed.     

Neuropsychological aspects of multiple sclerosis

Since S. Rao's ["Neuropsychology of Multiple Sclerosis: A Critical Review," A Journal of Clinical and Experimental Neuropsychology, Vol. 85, pp. 503-542] (1986) seminal review, considerable research has been undertaken on the neuropsychological consequences of multiple sclerosis. This review incorporates the research literature of the last decade in presenting an overview of the current state of our knowledge concerning the etiology, course, symptoms, assessment, consequences, and treatment of multiple sclerosis (MS). The concept of subcortical dementia is revisited in light of the most recent literature documenting the neuropsychological deficits in patients with MS. The view that cognitively heterogeneous patient groups may disguise more specific patterns of focal neuropsychological impairment is considered. A critical review of the recent literature is also presented, detailing the degree to which recent research has addressed the areas of research need identified by Rao in 1986. Given recent advances in our knowledge, the need for more attention to be directed toward the evaluation of rehabilitation and psychological intervention is highlighted.     

Non-specific immunosuppression and multiple sclerosis

Several series of arguments favor at least partial efficacy of immunosuppression in multiple sclerosis. Immunosuppression can often treat experimental autoimmune encephalitis, and imperfect model of multiple sclerosis. Certain agents have been shown to affect the pathophysiological processes seen indirectly on magnetic resonance imaging (mitoxantrone and Campath, for example). Therapeutic trials have their methodological weaknesses but do allow certain conclusions. The progressive forms of multiple sclerosis are the most widely studied. Massive but short-term immunosuppression does not appear to affect the course of progression but prolonged immunosuppression would appear to slow down the process, at least in responders. The effect on disease progression is modest and preference should go to well-tolerated treatments. Immunosuppression appears to effectively decrease the number of acute episodes and reduce the number of new lesions detectable by magnetic resonance imaging. The effect of immunosuppression is limited however by the fact that the clinical course of progressive forms depends less on the development of new lesions than on an aggravation of the demyelinization process and possible axon loss within constituted lesions. This is a further argument favoring early immunosuppressive treatment at a stage when it can be most effective.     

Genetic factors in multiple sclerosis

OBJECTIVE: To evaluate the role of candidate genes in the susceptibility to multiple sclerosis (MS) and describe the role of T-cell receptor (TCR) gene rearrangements in the MS brain lesion in identifying a major target of the immune response in this disease. DATA SOURCES: MEDLINE, bibliography review of published data, and unpublished studies. STUDY SELECTION: Published studies using novel molecular approaches to analyze the role of the major histocompatibility complex (MHC) and TCR gene complexes, as well as other candidate genes, in susceptibility to MS. We analyze epigenetic events involving TCR genes in individuals with MS and describe recent clinical trials in which immunotherapy has been attempted. DATA SYNTHESIS: Consistent with a polygenic model for disease predisposition, MHC and TCR gene associations with MS are relatively weak. Despite intensive research, no other putative "MS genes" have been firmly established. The analysis of TCR rearrangements in the brain lesion has helped to identify a major target of the immune response in MS. CONCLUSION: Understanding the genetic basis for autoimmune demyelination will offer new possibilities for the treatment of this illness.     

Clinical studies on multiple sclerosis

Nursery-reared rhesus monkeys were treated with no (n = 4) or moderate levels of lead (n = 4) during the first postnatal year. Mean blood lead levels peaked at 55 micrograms/dl at 5 weeks of age, averaged 36 micrograms/dl for the remainder of the first year postpartum, and declined to < or = 5 micrograms/dl for the 4 monkeys by 2.3 years of age. Previously, the lead-treated monkeys exhibited increased environmental exploration and decreased inactivity in a nonhuman primate version of the open field when tested at 4, 5, and 6 years of age (5,6). The current study was designed to assess behavior in the home cage of these monkeys at 6 years of age to determine: (a) whether the increased exploration was specific to the open field, and (b) any lead-related behavioral alterations specific to the home cage. Each monkey was observed twice weekly for 10 weeks and the duration and frequency of 17 behaviors were recorded. Lead treatment did not result in significant alterations in any of the six behaviors which occurred with enough frequency to warrant analysis. As a whole, all monkeys were either inactive or engaged in self-grooming for a large proportion of the test session. Less frequent were behaviors such as locomotion, environmental exploration, and self-directed behaviors. The distribution of behavioral activities in the home cage differed from that in the open field. Potential reasons for the expression of significant lead-related effects in the open field and not in the home cage are discussed as well as the differences in distribution of behavioral activities.     

Paroxysmal itching in multiple sclerosis

In three women with multiple sclerosis, paroxysmal attacks of itching occurred. There were several similarities between these attacks and other types of paroxysmal phenomena previously described in multiple sclerosis. The attacks were brief, but usually lasted several minutes, they started and ended abruptly, and recurred several times a day. The were controlled effectively by carbamazepine. It is suggested that paroxysmal itching is caused by transversely spreading ephaptic activation of axons within a partially demyelinated lesion in pain-conducting fibre tracts in the central nervous system.     

Current therapy of multiple sclerosis

There is no cure for multiple sclerosis (MS). Many therapeutic strategies are known. With exception of high dose corticosteroids for the treatment of acute exacerbations most of the concepts are not generally accepted. Reasons are the variable, often unpredictable natural course of MS, the incomplete understanding of the pathophysiology and the difficult trial design. Yet, new therapeutic agents give hope at least to slow the course of the disease.